Imidazolin-5-one derivative useful as FASN inhibitors for the treatment of cancer

ABSTRACT

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including those mediated by inhibition of fatty acid synthase (FASN) enzyme, such as, cancer, obesity or related discorders, and liver related disorders. Such compounds are represented by formula (I) as follows: 
                         
wherein L 1 , a, b, m, n, R 1 , R 2 , R 3 , R 4 , and R 5  are defined herein.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of U.S.application Ser. No. 14/020,122, filed on Sep. 6, 2013, currentlypending, and claims the benefit of U.S. Provisional Application No.61/698,125, filed Sep. 7, 2012, the entire disclosures of which arehereby incorporated in their entirety.

FIELD OF THE INVENTION

The present invention is directed to imidazolin-5-one derivatives,pharmaceutical compositions containing them, and their use as FASNinhibitors, in for example, the treatment of cancer, obesity relateddisorders, and liver related disorders.

BACKGROUND OF THE INVENTION

Fatty acid synthase (FASN) is a key enzyme for the synthesis oflong-chain fatty acids from acetyl-coenzyme A (CoA) and malonyl-CoA thatuses reduced nicotinamide adenine dinucleotidephosphate as a cofactor.The final step in the de novo synthesis of fatty acids in mammalians iscarried out by FASN, a 250 kDa protein containing 7 functional domains.Through an iterative enzymatic reaction, FASN produces palmitatestarting from the substrates acetylCoA and malonylCo, using NADPH (asdefined below) as a cofactor (See, MAIER, T., et al., “Architecture ofmammalian fatty acid synthase at 4.5 Å resolution”, Science, 2006, pp1258-1262, Vol. 311).

FASN is minimally expressed in most normal human tissues except theliver and adipose tissue, where it is expressed at high levels. Exceptfor these lipogenic tissues (such as liver, lactating breast, fetallung, and adipose tissue), FASN has a low expression in normal cellswhich use fatty acids from the diet, while tumor cells largely depend onde novo fatty acid synthesis. FASN expression is highly up-regulated invarious tumors, e.g. prostate, breast, colon, and lung cancer (See,SWINNEN, J. V., et al., “Stimulation of tumor-associated fatty acidsynthase expression by growth factor activation of the sterol regulatoryelement-binding protein pathway”. Oncogene, 2000, pp 5173-5181, Vol 19;KUHAJA, F. P., “Fatty-acid synthase and human cancer: new perspectiveson its role in tumor biology”, Nutrition, 2000, pp 202-208, Vol. 16).

FASN overexpression leads to growth and survival advantage to the tumorsachieved through multiple mechanisms. Firstly, it provides lipids formembrane synthesis. Moreover, the more saturated lipid composition ofthe membranes increases resistance to chemotherapy. FASN alsocontributes to improved growth factor receptor expression in lipid rafts(See, SWINNEN, J. V., et al., “Fatty acid synthase drives the synthesisof phospholipids partitioning into detergent resistant membranemicrodomains”, Biochem. Biophys. Res. Commun., 2000, pp 898-903, Vol.302; MENENDEZ, J. A., et al., “Inhibition of fatty acid synthase (FAS)suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells”,Proc. Natl Acad. Sci. USA, 2004, pp 10715-10720, Vol. 101), and improvedcell signalling. Lastly, the NAPDPH consumption during palmitatesynthesis in tumor cells keeps the redox balance in check.

In tumor cells, but not in normal cells, siRNA knock down orpharmacological inhibition of FASN results in apoptosis in vitro, and ina delayed tumor growth in vivo. The role of FASN as a potential oncogenehas been further established in mouse models. Transgenic mouse modelswith FASN over expression in the prostate develop invasive prostatecancer in the presence of Androgen Receptor (See, MIGITA, et al., “FattyAcid Synthase: A Metabolic Enzyme and Candidate Oncogene in ProstateCancer”, J Natl. Cancer Inst., 2009, pp 519-532, Vol. 101). It has beenproposed that FASN exerts its oncogenic effect by inhibiting theintrinsic pathway of apoptosis. Androgens and epidermal growth factor(EGF) up-regulate FASN expression and activity. In addition, FASN isalso over expressed in androgen-independent prostate cancers most likelythrough activation of the PI3K/Akt pathway (See, BANDYOPADHYAY, S., etal., “FAS expression inversely correlates with PTEN level in prostatecancer and a PI-3 kinase inhibitor synergizes with FAS siRNA to induceapoptosis”, Oncogene, 2005, pp 5389-5395, Vol. 24; VAN DE DANDE, T., etal., “Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathwayin the overexpression of fatty acid synthase in LNCaP prostate cancercells”, Cancer Res., 2002, pp 642-646, Vol. 62; PORTSMANN, T., et al.,“PKB/AKT induces transcription of enzymes involved in cholesterol andfatty acid biosynthesis via activation of SREBP”, Oncogene, 2005, pp6465-6481, Vol. 24). Thus, FASN is emerging as an important target forcancer therapy.

Since FASN expression is markedly increased in several human cancerscompared with the corresponding normal tissue, and FASN overexpressionin tumors has been associated with a poor prognosis, FASN inhibitors areviewed as potential therapeutics for the treatment of cancer. Thereremains a need for pharmaceutical agents for the treatment of a varietyof cancers, including breast, prostate, head, neck, skin, lung, ovary,endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver,bladder, pancreas, brain, blood, bone, and others.

FASN inhibitors have also shown promise in the treatment of otherFASN-mediated diseases, disorders or conditions, such as, obesity, lackof appetite control, and inflammatory conditions. Additionally, FASN hasbeen implicated in diabetes and/or regulation of the general wellness ofthe liver, and therefore has potential in the treatment of obesity, TypeII diabetes mellitus, Syndrome X, and disorders of the liver; thetreatment of which there remains a need for pharmaceutical agents.

SUMMARY OF THE INVENTION

The present invention is directed to compounds of formula (I)

wherein

R¹ and R² are taken together with the carbon atom to which they arebound to form an optionally substituted ring structure selected from thegroup consisting of

(a) C₃₋₈cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substitutedwith one to two R¹ groups;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkylis bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ringstructure; wherein the benzo-fused C₅₋₆cycloalkyl is optionallysubstituted with one to two R¹¹ groups;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to8-membered, saturated heterocyclyl contains one heteroatom selected fromthe group consisting of O, S and N; wherein the S is optionallysubstituted with one to two oxo; wherein the N is substituted with R¹⁰;provided that the heteroatom is not present at the 2-position relativeto the carbon atom of the imidazolin-5-one; and wherein the 4 to8-membered, saturated heterocyclyl is optionally substituted with oneR¹¹ group, and further optionally substituted with one R¹² group;

wherein R¹⁰ is selected from the group consisting of hydrogen,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl),—(C₂₋₄alkyl)-O—(C₁₋₅alkyl), —(C₂₋₄alkenyl), —(C₁₋₄ alkyl)-phenyl,—C(O)—NR^(A)R^(B), —C(O)—(C₁₋₃alkyl)-NR^(A)R^(B), —C(O)—(C₁₋₄alkyl),—C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl), —C(O)-phenyl,—C(O)-(5 to 6-membered heteroaryl),

—C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(A)R^(B), phenyl and 5 to6-membered heteroaryl;

wherein Z¹ is selected from the group consisting of —CH₂—, —O—,—N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(A), R^(B) and R^(C) areeach independently selected from the group consisting of hydrogen andC₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or aspart of a substituent group, is further optionally substituted with oneto two substituents independently selected from the group consisting ofhalogen, hydroxy, cyano, NR^(A)R^(B), C₁₋₄alkyl, fluorinated C₁₋₄alkyl,C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

-   -   wherein each R¹¹ is independently selected from the group        consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated        C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy        substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl),        —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E),        —C(O)—(C₁₋₄alkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered        heteroaryl),

—C(O)OH, —C(O)O—(C₁₋₄ alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(D)R^(E), phenyland 5 to 6-membered heteroaryl;

wherein Z² is selected from the group consisting of —CH₂—, —O—,—N(R^(C))—, S—, —S(O)— and —SO₂—; wherein R^(D), R^(E) and R^(F) areeach independently selected from the group consisting of hydrogen andC₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl, whether alone oras part of a substituent group, is further optionally substituted withone to two substituents independently selected from the group consistingof halogen, hydroxy, cyano, NR^(D)R^(E), C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

-   -   and wherein R¹² is selected from the group consisting of        hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄ alkyl,        C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and hydroxy substituted        C₁₋₄alkyl;    -   m is an integer from 0 to 1; and n is an integer from 0 to 2;        provided that when n is 2, then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl,piperidin-2S-yl, and piperidin-4-yl;

-   -   a is an integer from 0 to 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O—,—C(O)—NR^(L), —C(S)—, —SO₂—, —SO₂—NR^(L)—; wherein R^(L) is selectedfrom the group consisting of hydrogen and C₁₋₄alkyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl,—(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), 4 to 6-membered, saturated heterocyclyl,—(C₁₋₄alkyl)-(4 to 6-membered, saturated heterocyclyl),—(C₂₋₄alkenyl)-(5 to 6-membered, saturated heterocyclyl), 5 to6-membered heteroaryl, —(C₁₋₄alkyl)-(5 to 6-membered heteroaryl),—(C₂₋₄alkenyl)-(5 to 6-membered heteroaryl), and NR^(V)R^(W); whereinR^(V) and R^(W) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl;

wherein the C₃₋₆cycloalkyl, 4 to 6-membered saturated heterocyclyl or 5to 6-membered heteroaryl, whether alone or as part of a substituentgroup, is optionally substituted with one to two substituentsindependently selected from the group consisting of halogen, hydroxy,cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₄alkyl)-OH, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy, and NR^(G)R^(H): wherein R^(G) and R^(H) areeach independently selected from the group consisting of hydrogen andC₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 2;

each R⁴ is independently selected from the group consisting of hydroxy,halogen, C₁₋₄alkyl, fluorinated C₁₋₄ alkyl, C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, cyano, and NR^(J)R^(K); wherein R^(J) and R^(K) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl; provided that each R⁴ group is bound to a carbon atom;

provided that when

is selected from the group consisting of

and substituted with —(R⁴)_(b), then b is an integer from 0 to 1;

R⁵ is selected from the group consisting of

wherein

selected from the group consisting of aryl, heteroaryl and partiallyunsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy,oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, —(C₁₋₄alkyl)-CN, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl),C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —NR^(M)R^(N),—(C₁₋₄alkyl)-NR^(P)R^(Q), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinatedC₁₋₂alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl),—NR^(M)—C(O)H, —NR^(M)—C(O)—(C₁₋₄alkyl), —NR^(M)—SO₂—(C₁₋₄ alkyl),C₃₋₆cycloalkyl, -cyano-(C₃₋₆-(cycloalkyl),—(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), —S—(C₃₋₆cycloalkyl),—SO—(C₃₋₆cycloalkyl), —SO₂(C₃₋₆cycloalkyl), —NH—(C₃₋₆cycloalkyl),—NH—SO₂—(C₃₋₆cycloalkyl), oxetanyl, —(C₁₋₂alkyl)-oxetanyl,tetrahydofuranyl, —(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl,and —(C₁₋₂alkyl)-tetrahydro-pyranyl;

wherein R^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl;

wherein R^(P) and R^(Q) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl; alternatively R^(P) and R^(Q) aretaken together with the nitrogen atom to which they are bound to form a5 to 6-membered saturated heterocyclyl; such 5 to 6-membered saturatedheterocyclyl is optionally substituted with a substituent selected fromthe group consisting of halogen, C₁₋₄alkyl and fluorinated C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano,nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl,C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(R)R^(S), —C(O)—NR^(R)R^(S),—C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R^(R) and R^(S) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

wherein

is selected from the group consisting of phenyl, 5 to 6-memberedsaturated heterocyclyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy,halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U),—C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl),—(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl),oxetanyl, —(C₁₋₂alkyl)-oxetanyl, tetrahydofuranyl,—(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl and—(C₁₋₂alkyl)-tetrahydro-pyranyl; wherein R^(T) and R^(U) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

provided that when R¹ and R² are taken together with the carbon atom towhich they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)₃-R³ is selected from the group consisting of—C(O)—CF, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃ or—SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl,1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl,4-(1-methyl-pyrazol-4-yl)-phenyl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl) and1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopentyl; m is 1 and n is 0 or mis 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl,2-(piperazin-1-yl)-pyridin-4-yl and2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopentyl; m is 1 and n is 0 or mis 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl,1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl,indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl,6-(1-cyanomethyl)-pyridin-3-yl,6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl,3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl,4-(1-isobutyl-pyrazol-5-yl)-phenyl or 6-(morpholin-4-yl)-pyridin-3-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is—C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl,benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl or4-(3-chlorophenyl)-phenyl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl,1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or4-(1-methyl-pyrazol-4-yl)-phenyl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0 and n is 1 or mis 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl,2-oxo-3,4-dihydro-quinolin-7-yl or6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;

provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form tetrahydrofuran-3,3-diyl ortetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl,benzofuran-5-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl;

and stereoisomers, tautomers, and pharmaceutically acceptable saltsthereof.

The present invention is further directed to processes for thepreparation of the compounds of formula (I), as described in more detailin the general synthesis schemes and examples below. The presentinvention is further directed to a product prepared according to any ofthe processes as described in the general synthesis schemes and examplesbelow.

The present invention is further directed to intermediates in thesynthesis of the compounds of formula (I), including, but not limitedto, compounds of formula (XVII), compounds of formula (XXI), compoundsof formula (XXIlI), compounds of formula (XXV) and compounds of formula(XXVII), as described in more detail below.

Illustrative of the invention is a pharmaceutical compositioncomprising, consisting of and/or consisting essentially of apharmaceutically acceptable carrier and the product prepared accordingto the process described herein. An illustration of the invention is apharmaceutical composition made by mixing the product prepared accordingto the process described herein and a pharmaceutically acceptablecarrier. Illustrating the invention is a process for making apharmaceutical composition comprising, consisting of, and/or consistingessentially of mixing the product prepared according to the processdescribed herein and a pharmaceutically acceptable carrier.

Exemplifying the invention are methods of treating a disorder mediatedby inhibition of fatty acid synthase (FASN) enzyme (selected from thegroup consisting of cancer, obesity and related disorders, and liverrelated disorders, as defined below) comprising, consisting of, and/orconsisting essentially of administering to a subject in need thereof atherapeutically effective amount of any of the compounds orpharmaceutical compositions described above.

In an embodiment, the present invention is directed to a compound offormula (I) for use as a medicament. In another embodiment, the presentinvention is directed to a compound of formula (I) for use in thetreatment of a disorder mediated by inhibition of fatty acid synthase(FASN) enzyme (selected from the group consisting of cancer, obesity andrelated disorders, and liver related disorders, as defined below). Inanother embodiment, the present invention is directed to a compositioncomprising a compound of formula (I) for the treatment of a disordermediated by inhibition of fatty acid synthase (FASN) enzyme (selectedfrom the group consisting of cancer, obesity and related disorders andliver related disorders, as herein below).

Another example of the invention is the use of any of the compoundsdescribed herein in the preparation of a medicament for treating: (a)cancer, as defined below, (b) obesity or related disorder, (c) liverrelated disorder, in a subject in need thereof.

In another example, the present invention is directed to a compound asdescribed herein for use in a methods for treating a disorder selectedfrom the group consisting of cancer, obesity and related disorders, andliver related disorders, as herein defined, in a subject in needthereof,

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to compounds of formula (I)

wherein R¹, R², R³, R⁴, R⁵, L¹, a, b, m, n, and

are as herein defined. The compounds of the present invention are FASNinhibitors useful in the treatment of, for example, cancer. Moreparticularly, the compounds of formula (I) of the present invention areuseful in the treatment of FASN-mediated disorders including, but notlimited to, (a) cancer, as herein defined, (b) obesity and relateddisorders and (c) liver related disorders, as herein defined.

In a preferred embodiment, the present invention is directed to methodsfor the treatment of cancer comprising, consisting of, and/or consistingessentially of administering to a subjected in need thereof, atherapeutically effective amount of a compound of formula (I); whereinthe cancer is selected from the group consisting of cancer of thebreast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid,colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas,brain, spinal cord, blood, and bone. Preferably, the cancer is selectedfrom the group consisting of breast, prostate, colon, lung, brain,spinal cord, ovary, endometrium, thyroid, kidney, and stomach.

In another embodiment, the cancer is selected from the group consistingof glioma, glioblastoma, leukemia, Bannayan-Zonana syndrome, Cowdendisease, Lhermitte-Duclos disease, breast cancer, inflammatory breastcancer, Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma, ependymoma,medulloblastoma, sarcoma, osteosarcoma, melanoma, giant cell tumor ofbone, and giant cell tumor of thyroid.

In another embodiment, the present invention is directed to methods forthe treatment of obesity or a related disorder comprising, consistingof, and/or consisting essentially of administering to a subjected inneed thereof, a therapeutically effective amount of a compound offormula (I); wherein the obesity or related disorder is selected fromthe group consisting of obesity, overweight, weight gain, Type IIdiabetes mellitus, Syndrome X, appetite and/or satiety modulation.Preferably, the obesity or related disorders is selected from the groupconsisting of obesity, Type II diabetes mellitus, Syndrome X, andappetite and/or satiety modulation, more preferably obesity or Type IIdiabetes mellitus.

In another embodiment, the present invention is directed to methods forthe treatment of an liver related disorder comprising, consisting of,and/or consisting essentially of administering to a subjected in needthereof, a therapeutically effective amount of a compound of formula(I); wherein the liver related disorder is selected from the groupconsisting of dyslipidemia, elevated cholesterol levels, elevated LDL,decreased HDL, elevated triglicerides, fatty liver, non-alcoholicsteatohepatitis (NASH), fatty liver, and/or non-alcoholic fatty liverdisease (NAFLD). Preferably, the liver related disorder is selected fromdylipidemia or elevated cholesterol levels.

In an embodiment, the present invention is directed to a pharmaceuticalcomposition comprising, consisting of, and/or consisting essentially ofa pharmaceutically acceptable carrier and a compound of formula (I). Inanother embodiment, the present invention is directed to apharmaceutical composition made by mixing a compound of formula (I) anda pharmaceutically acceptable carrier. In another embodiment, thepresent invention is directed to a process for making a pharmaceuticalcomposition comprising mixing a compound of formula (I) and apharmaceutically acceptable carrier.

In an embodiment, the present invention is directed to a method oftreating a disorder mediated by inhibition of fatty acid synthase (FASN)enzyme, comprising, consisting of, and/or consisting essentially ofadministering to a subject in need thereof a therapeutically effectiveamount of the compound of formula (I).

In another embodiment, the present invention is directed to a method oftreating a disorder mediated by inhibition of fatty acid synthase (FASN)enzyme, wherein the disorder mediated by inhibition of fatty acidsynthase (FASN) enzyme is a cancer selected from the group consisting ofthe breast, prostate, head, neck, skin, lung, ovary, endometrium,thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder,pancreas, brain, spinal cord, blood, and bone.

In another embodiment, the present invention is directed to a method oftreating a disorder mediated by inhibition of fatty acid synthase (FASN)enzyme, wherein the disorder mediated by inhibition of fatty acidsynthase (FASN) enzyme is selected from the group consisting of obesity,overweight, weight gain, Type II diabetes mellitus, Syndrome X, andappetite or satiety modulation.

In another embodiment, the present invention is directed to a method oftreating a disorder mediated by inhibition of fatty acid synthase (FASN)enzyme, wherein the disorder mediated by inhibition of fatty acidsynthase (FASN) enzyme is selected from the group consisting ofdyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL,elevated triglicerides, fatty liver, non-alcoholic steatohepatitis(NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD).

In an embodiment, the present invention is directed to a method oftreating (a) cancer of the breast, prostate, head, neck, skin, lung,ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney,liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesityor a related disorder selected from the group consisting of obesity,overweight, weight gain, Type II diabetes mellitus, Syndrome X, andappetite or satiety modulation; or (c) a liver related disordersselected from the group consisting of dyslipidemia, elevated cholesterollevels, elevated LDL, decreased HDL, elevated triglicerides, fattyliver, non-alcoholic steatohepatitis (NASH), fatty liver andnon-alcoholic fatty liver disease (NAFLD); comprising, consisting of,and/or consisting essentially of administering to a subject in needthereof, a therapeutically effective amount of the compound of formula(I).

In another embodiment, the present invention is directed to a method oftreating (a) cancer of the breast, prostate, head, neck, skin, lung,ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney,liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesityor a related disorder selected from the group consisting of obesity,overweight, weight gain, Type II diabetes mellitus, Syndrome X, andappetite or satiety modulation; or (c) a liver related disordersselected from the group consisting of dyslipidemia, elevated cholesterollevels, elevated LDL, decreased HDL, elevated triglicerides, fattyliver, non-alcoholic steatohepatitis (NASH), fatty liver andnon-alcoholic fatty liver disease (NAFLD); comprising, consisting of,and/or consisting essentially of administering to a subject in needthereof a therapeutically effective amount of a pharmaceuticalcomposition comprising a compound of formula (I).

In an embodiment, the present invention is directed to the use of acompound formula (I) for the preparation of a medicament for treating:(a) cancer of the breast, prostate, head, neck, skin, lung, ovary,endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver,bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or arelated disorder selected from the group consisting of obesity,overweight, weight gain, Type II diabetes mellitus, Syndrome X, andappetite or satiety modulation; or (c) a liver related disordersselected from the group consisting of dyslipidemia, elevated cholesterollevels, elevated LDL, decreased HDL, elevated triglicerides, fattyliver, non-alcoholic steatohepatitis (NASH), fatty liver andnon-alcoholic fatty liver disease (NAFLD); in a subject in need thereof.

In another embodiment, the present invention is directed to the use of acompound of formula (I), for use in a method for treating a disorderselected from the group consisting of (a) cancer of the breast,prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon,rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain,spinal cord, blood or bone; (b) obesity or a related disorder selectedfrom the group consisting of obesity, overweight, weight gain, Type IIdiabetes mellitus, Syndrome X, and appetite or satiety modulation; or(c) a liver related disorders selected from the group consisting ofdyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL,elevated triglicerides, fatty liver, non-alcoholic steatohepatitis(NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD); in asubject in need thereof.

In another embodiment, the present invention is directed to a compoundof formula (I) for use as a medicament. In another embodiment, thepresent invention is directed to a compound of formula (I) (as in Claim1) for use in the treatment of a disorder mediated by inhibition offatty acid synthase (FASN) enzyme. In another embodiment, the presentinvention is directed to a compound of formula (I), for use in thetreatment of a disorder mediated by inhibition of fatty acid synthase(FASN) enzyme, selected from the group consisting of cancer of thebreast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid,colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas,brain, spinal cord, blood or bone. In another embodiment, the presentinvention is directed to a compound of formula (I), for use in thetreatment of a disorder mediated by inhibition of fatty acid synthase(FASN) enzyme, selected from (a) obesity and related disorders or (b)liver related disorders.

In an embodiment, the present invention is directed to a compositioncomprising, consisting of, and/or consisting essentially of a compoundof formula (I) for use in the treatment of a disorder mediated byinhibition of fatty acid synthase (FASN) enzyme.

In another embodiment, the present invention is directed to acomposition comprising, consisting of, and/or consisting essentially ofcompound of formula (I) for use in the treatment of a disorder mediatedby inhibition of fatty acid synthase (FASN) enzyme selected from thegroup consisting of (a) cancer of the breast, prostate, head, neck,skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus,stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood orbone; (b) obesity or a related disorder selected from the groupconsisting of obesity, overweight, weight gain, Type II diabetesmellitus, Syndrome X, and appetite or satiety modulation; and (c) aliver related disorders selected from the group consisting ofdyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL,elevated triglicerides, fatty liver, non-alcoholic steatohepatitis(NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD).

In an embodiment, the present invention is directed to compounds offormula (I)

wherein

R¹ and R² are taken together with the carbon atom to which they arebound to form an optionally substituted ring structure selected from thegroup consisting of

(a) C₃₋₈cycloalkyl; wherein the C₃₋₆cycloalkyl is optionally substitutedwith one to two R¹¹ groups;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkylis bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ringstructure; wherein the benzo-fused C₅₋₆cycloalkyl is optionallysubstituted with one to two R¹¹ groups;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to8-membered, saturated heterocyclyl contains one heteroatom selected fromthe group consisting of O, S and N; wherein the S is optionallysubstituted with one to two oxo; wherein the N is substituted with R¹⁰;provided that the heteroatom is not present at the 2-position relativeto the carbon atom of the imidazolin-5-one; and wherein the 4 to8-membered, saturated heterocyclyl is optionally substituted with oneR¹¹ group, and further optionally substituted with one R¹² group;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl),—(C₂₋₄alkyl)-O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B),—C(O)—(C₁₋₃alkyl)-NR^(A)R^(B), —C(O)—(C₁₋₄alkyl),—C(O)—(C₃₋₆cycloalkyl), —C(O)-phenyl, —C(O)-(5 to 6-memberedheteroaryl),

—C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(A)R^(B), phenyl and 5 to6-membered heteroaryl;

wherein Z¹ is selected from the group consisting of —CH₂—, —O—,—N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(A), R^(B) and R^(C) areeach independently selected from the group consisting of hydrogen andC₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or aspart of a substituent group, is further optionally substituted with oneto two substituents independently selected from the group consisting ofhalogen, hydroxy, cyano, NR^(A)R^(B), C₁₋₄alkyl, fluorinated C₁₋₄alkyl,C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein each R¹¹ is independently selected from the group consisting ofhydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl,—(C₁₋₄alkyl)-O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E),—C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)-phenyl, —C(O)-(5 to6-membered heteroaryl),

—C(O)OH, —C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(D)R^(E), phenyland 5 to 6-membered heteroaryl;

-   -   wherein Z² is selected from the group consisting of —CH₂—, —O—,        —N(R^(C))—, S—, —S(O)— and —SO₂—; wherein R^(D), R^(E) and R^(F)        are each independently selected from the group consisting of        hydrogen and C₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or aspart of a substituent group, is further optionally substituted with oneto two substituents independently selected from the group consisting ofhalogen, hydroxy, cyano, NR^(D)R^(E), C₁₋₄alkyl, fluorinated C₁₋₄alkyl,C₁₋₄alkoxy, and fluorinated C₁₋₄alkoxy;

and wherein R¹² is selected from the group consisting of hydroxy, oxo,halogen, C₁₋₄alkyl, fluorinated C₁₋₄ alkyl, C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, and hydroxy substituted C₁₋₄alkyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, and piperidin-4-yl;

a is an integer from 0 to 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)—NR^(L)—,—C(S)—, —SO₂—, and —SO₂—NR^(L)—; wherein R^(L) is selected from thegroup consisting of hydrogen and C₁₋₄alkyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₈cycloalkyl, —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), 5to 6-membered, saturated heterocyclyl, —(C₁₋₄ alkyl)-(5 to 6-membered,saturated heterocyclyl), —(C₂₋₄alkenyl)-(5 to 6-membered, saturatedheterocyclyl), 5 to 6-membered heteroaryl, —(C₁₋₄alkyl)-(5 to 6-memberedheteroaryl), and —(C₂₋₄alkenyl)-(5 to 6-membered heteroaryl);

wherein the C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl or 5to 6-membered heteroaryl, whether alone or as part of a substituentgroup, is optionally substituted with one to two substituentsindependently selected from the group consisting of halogen, hydroxy,cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 2;

each R⁴ is independently selected from the group consisting of hydroxy,halogen, C₁₋₄ alkyl, fluorinated C₁₋₄alkyl, C₁₋₄ alkoxy, fluorinatedC₁₋₄alkoxy, cyano, and NR^(J)R^(K); wherein R^(J) and R^(K) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl; provided that each R⁴ group is bound to a carbon atom;

provided that when

is selected from the group consisting of

and substituted with —(R⁴)_(b), then b is an integer from 0 to 1;

R⁵ is selected from

wherein

selected from the group consisting of aryl, heteroaryl, and partiallyunsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy,halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(M)R^(N),—(C₁₋₄alkyl)-NR^(P)R^(Q), —C(O)—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —C(O)OH,—C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, —NR^(M)—C(O)—(C₁₋₄alkyl), and—NR^(M)—SO₂—(C₁₋₄alkyl);

wherein R^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl;

wherein R^(P) and R^(Q) are each independently selected from hydrogen orC₁₋₄ alkyl; alternatively R^(P) and R^(Q) are taken together with thenitrogen atom to which they are bound to form a 5 to 6-memberedsaturated heterocyclyl; such 5 to 6-membered saturated heterocyclyl isoptionally substituted with a substituent selected from the groupconsisting of halogen, C₁₋₄alkyl, and fluorinated C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano,nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl,C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(R)R^(S), —C(O)—NR^(R)R^(S),—C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R^(R) and R^(S) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy,halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U),—C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and—(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are each independentlyselected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

and a stereoisomer, a tautomer, and a pharmaceutically acceptable saltthereof.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ringstructure selected from the group consisting of

(a) C₃₋₆cycloalkyl; wherein the C₃₋₅cycloalkyl is optionally substitutedwith one R¹¹ group;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkylis bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ringstructure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionallysubstituted with one R¹¹ group; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to6-membered, saturated heterocyclyl contains O or NR¹⁰; provided that theO or NR¹⁰ is not present at the 2-position relative to the carbon atomof the imidazolin-5-one; and wherein the 4 to 6-membered, saturatedheterocyclyl containing the O or NR¹⁰ is optionally substituted with oneR¹ group and further optionally substituted with one R¹²;

wherein R¹⁰ is selected from the group consisting of hydrogen,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, CH₂-(hydroxy substituted C₁₋₄alkyl),—(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —(C₂alkyl)-O—(C₁₋₄alkyl),—C(O)O—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl),—C(O)—(C₃₋₆cycloalkyl),

—C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl); wherein Z¹ is selected from thegroup consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B)and R^(C) are each independently selected from the group consisting ofhydrogen and C₁₋₄alkyl;

-   -   wherein R¹¹ is independently selected from the group consisting        of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl,        C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted        C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E),        —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and        —C(O)O—(C₁₋₄alkyl);

wherein R¹² is selected from the group consisting of hydroxy, oxo,halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substitutedC₁₋₂alkyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2; providedthat when n is 2, then m is 0;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl,piperidin-3R-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O—,—C(O)—NR^(L)— and —SO₂—; wherein R^(L) is selected from the groupconsisting of hydrogen and methyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinatedC₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, 4to 6-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl andNR^(V)R^(W); wherein R^(V) and R^(W) are each independently selectedfrom the group consisting of hydrogen and C₁₋₂alkyl;

wherein the C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5to 6-membered heteroaryl, is optionally substituted with one to twosubstituents independently selected from the group consisting ofhalogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl,—(C₁₋₂alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(G)R^(H);wherein R^(G) and R^(H) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl,fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy andNR^(J)R^(K); wherein R^(J) and R^(K) are each independently selectedfrom the group consisting of hydrogen and C₁₋₂alkyl; provided that theR⁴ group is bound to a carbon atom;

-   -   R⁵ is selected from the group consisting of

wherein

selected from the group consisting of aryl, heteroaryl and partiallyunsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy,oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, cyano substituted (C₁₋₄alkyl),—(C₁₋₂alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy,—SO₂—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl),—C(O)OH, —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N),—NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₅cycloalkyl,1-cyano-(C₃₋₅cycloalkyl), —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl),—S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloakyl), —NH—(—C₃₋₅cycloalkyl),—NH—SO₂—(C₃₋₅cycloalkyl), oxetanyl and tetrahydro-furanyl;

wherein R^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl; wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl,C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein

is selected from the group consisting of phenyl, 5 to 6-memberedsaturated heterocyclyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy,halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substitutedC₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U),—C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl),—(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl),oxetanyl, and tetrahydro-furanyl; wherein R^(T) and R^(U) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ringstructure selected from the group consisting of

(a) C₃₋₆cycloalkyl; wherein the C₃₋₆cycloalkyl is optionally substitutedwith one R¹¹ group;

(b) benzo-fused C₃₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkylis bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ringstructure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionallysubstituted with one R¹¹ group;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to8-membered, saturated heterocyclyl contains O or NR¹⁰; provided that theO or NR¹⁰ is not present at the 2-position relative to the carbon atomof the imidazolin-5-one; and wherein the 4 to 8-membered, saturatedheterocyclyl containing the O or NR¹⁰ is optionally substituted with oneR¹¹ group and further optionally substituted with one R¹²;

wherein R¹⁰ is selected from the group consisting of hydrogen,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl),—(—C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₄alkyl),—C(O)—(C₃₋₆cycloalkyl),

wherein Z¹ is selected from the group consisting of —CH₂—, —O— and—N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independentlyselected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein R¹¹ is independently selected from the group consisting ofhydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl,—(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E),—C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄alkyl);

wherein R¹² is selected from the group consisting of hydroxy, oxo,halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substitutedC₁₋₂alkyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)—NR^(L)— and—SO₂—; wherein R^(L) is selected from the group consisting of hydrogenand methyl;

R³ is selected from the group consisting of C₂₋₄alkenyl, C₃₋₆cycloalkyl,5 to 6-membered, saturated heterocyclyl and 5 to 6-membered heteroaryl;

wherein the C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl or 5to 6-membered heteroaryl, is optionally substituted with one to twosubstituents independently selected from the group consisting ofhalogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy and NR^(G)R^(H); wherein R^(G) and R^(H) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl,fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy andNR^(J)R^(K); wherein R^(J) and R^(K) are each independently selectedfrom the group consisting of hydrogen and C₁₋₂alkyl; provided that theR⁴ group is bound to a carbon atom;

R⁵ is selected from the group consisting of

-   -   wherein

selected from the group consisting of aryl, heteroaryl and partiallyunsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy,halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(M)R^(N),—C(O)—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl),—NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₄alkyl);

wherein R^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl,C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein

is selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy,halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substitutedC₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U),—C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and—(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are each independentlyselected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ringstructure selected from the group consisting of

(a) C₃₋₆cycloalkyl; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-memberedsaturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is notpresent at the 2-position relative to the carbon atom of theimidazolidin-5-one;

wherein R¹⁰ is selected from the group consisting of hydrogen,C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxy substituted C₁₋₂alkyl),—CH₂-(phenyl), —(C₂alkyl)-O—(C₁₋₂alkyl), —C(O)—(C₁₋₄alkyl),—C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl), —C(O)O—(C₁₋₄alkyl),—C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl), wherein R^(A) and R^(B) are eachindependently selected from the group consisting of hydrogen and methyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2 providethat when n is 2, then m is 0

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl,piperidin-3S-yl, and piperidin-4-yl;

-   -   a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of C₁₋₄alkyl, hydroxysubstituted C₁₋₄alkyl, fluorinated C₁₋₂alkyl, C₂₋₄alkenyl,C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl, 5 to 6-memberedheteroaryl and NR^(V)R^(W); wherein the C₃₋₅cycloalkyl, 4 to 5-membered,saturated heterocyclyl or 5 to 6-membered heteroaryl is optionallysubstituted with a substituent selected from the group consisting ofhalogen, hydroxy, C₁₋₂alkyl, (C₁₋₂alkyl)-OH, fluorinated C₁₋₂alkyl,cyano and NH₂; and wherein R^(V) and R^(W) are each independentlyselected from the group consisting of hydrogen and methyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl andC₁₋₂alkoxy;

R⁵ is selected from the group consisting of

wherein

selected from the group consisting of phenyl, naphthyl, 5 to 6-memberedheteroaryl, 9 to 10-membered heteroaryl and partially unsaturated 9 to10-membered heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy,oxo, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxysubstituted C₁₋₄alkyl, cyano-substituted C₁₋₂alkyl,—(C₁₋₂alkyl)-O—(C₁₋₂alkyl), C₁₋₄alkoxy, fluorinated C₁₋₂alkoxy,—SO₂—(C₁₋₄alkyl), —CO²H, —C(O)O—(C₁₋₂alkyl), —C(O)—(C₁₋₂alkyl),—C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N),—NR^(M)—C(O)H, —R^(M)—SO₂—(C₁₋₂alkyl), C₃₋₅ cycloalkyl,1-cyano-cyclopropyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl,—S—(C₃₋₅cycloalkyl), —SO₂alkyl)-NH—C(O)—(C₃₋₅cycloalkyl) and—NH—SO₂—(C₃₋₅cycloalkyl) and oxetan-3-yl; and wherein R^(M) and R^(N)are each independently selected from the group consisting of hydrogenand C₁₋₂alkyl;

wherein

is selected from the group consisting of phenyl and 6-membered, nitrogencontaining heteroaryl;

wherein

is selected from the group consisting of phenyl, 5 to 6-membered,saturated, nitrogen containing heterocyclyl and 5 to 6-membered,nitrogen containing heteroaryl;

e is an integer from 0 to 1;

R⁸ is selected from the group consisting of halogen, C₁₋₄alkyl,C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl) and oxetanyl;

provided that the

is bound at the 3- or 4-position of the

relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein,

R¹ and R² are taken together to form an optionally substituted ringstructure selected from the group consisting of

(a) C₃₋₆cycloalkyl; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-memberedsaturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is notpresent at the 2-position relative to the carbon atom of theimidazolidin-5-one; wherein R¹⁰ is selected from the group consisting ofhydrogen, C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₂alkyl),—CH₂-(phenyl), —C(O)—(C₁₋₄alkyl), —C(O)-(cyclopropyl) and—C(O)—NR^(A)R^(B); wherein R^(A) and R^(B) are each independentlyselected from the group consisting of hydrogen and methyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)— and —SO₂—;

R³ is selected from the group consisting of C₂alkenyl, C₃cycloalkyl,5-membered, saturated heterocyclyl and 5-membered heteroaryl; whereinthe C₃cycloalkyl, 5-membered, saturated heterocyclyl or 5-memberedheteroaryl is optionally substituted with a substituent selected fromthe group consisting of halogen, C₁₋₂alkyl, fluorinated C₁₋₂alkyl andcyano;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl andC₁₋₂alkoxy;

R⁵ is selected from the group consisting of

wherein

selected from the group consisting of phenyl, heteroaryl and partiallyunsaturated heterocyclyl;

c is an integer from 0 to 2;

-   -   each R⁶ is independently selected from the group consisting of        hydroxy, halogen, cyano, C₁₋₂alkyl, fluorinated C₁₋₂alkyl,        C₁₋₂alkoxy, fluorinated C₁₋₂alkoxy, —NR^(M)R^(N),        —C(O)—(C₁₋₂alkyl), —NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₂alkyl);        and wherein R^(M) and R^(N) are each independently selected from        the group consisting of hydrogen and C₁₋₂alkyl;

wherein

is phenyl;

wherein

is selected from the group consisting of phenyl and 5 to 6-membered,nitrogen containing heteroaryl;

e is an integer from 0 to 1;

R⁸ is selected from the group consisting of halogen and C₁₋₂alkyl;

provided than when

is phenyl, then

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl,1-(ethenyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl and1-(methoxycarbonyl)-azetidin-3,3-diyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2; providedthat when n is 2 then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3R-yl, piperidin-3S-yl andpiperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of methyl, ethyl, isopropyl,1-hydroxyethyl, trifluoromethyl, 2,2,2-trifluoroethyl,2-hydroxy-propan-2-yl. 3-hydroxy-2-methyl-propan-2-yl, ethenyl,cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl,1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino,dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl,tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl,3-methyl-oxetan-3-yl, and pyridin-3-yl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 3-fluoro,2-chloro, 3-chloro, 2-methyl, 3-methyl and 2-methoxy;

R⁵ is selected from the group consisting of

wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl,3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl,2-fluoro-4-(1-cyano-cuclopropyl)-phenyl,2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl,3-(cyclopropylcarbonyl-amino)-phenyl,3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl,3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl,3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl,6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl,7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl,1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl,pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl,6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl,5-(2-hydroxy-2-methyl-propyl-propyl)-pyridin-3-yl,6-cyclopropyl-pyridin-3-yl, 6-(1-cyano-cyclopropyl)-pyridin-3-yl,2-amino-pyrid-4-yl, 5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl,1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl,indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl,2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl,1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl,1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl,quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl,quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl,2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl,2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl,2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl,2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl,2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl,3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl,4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl,2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl,2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl,3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl,6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl,3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl,3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl,quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl,1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl,1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl,1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl,1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl,2-(2-hydroxyethyl)-6-fluoroindazol-5-yl, 1-methyl-3-chloro-indazol-5-yl,1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-5-yl,1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-7-methoxymethyl-indazol-4-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-7-hydroxymethyl-indazol-4-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl,2-methyl-3-hydroxymethyl-indazol-5-yl,2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl,2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl,2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl,1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl,2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl,2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl,1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl,benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl,benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl,2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, 2,3-dihydro-benzofuran-5-yl,2-oxo-3,4-dihydro-quinolin-7-yl,1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl,1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl,2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl,pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl,[1,2,4]triazo[4,3-a]pyridin-6-yl,3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl and4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl;

is selected from the group consisting of phenyl, pyridin-3-yl andpyridin-4-yl;

and

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl,1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl,pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl,piperazin-1-yl, 4-methyl-piperazin-1-yl, and1-(oxetan-3-yl)-pyrazol-4-yl;

provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the point of attachment of the

to the

provided further that when

is pyridin-4-yl, then

is bound to

at the 3-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein,

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl; a is 1; L¹ isselected from the group consisting of —C(O)— and —SO₂—; R³ is selectedfrom the group consisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl and tetrahydro-furan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro, 2-methyl, 3-methyl and 2-methoxy; R⁵ is selected from thegroup consisting of

wherein

is selected from the group consisting of 4-(3-cyano-phenyl),4-(4-cyano-phenyl), 4-(3-hydroxy-phenyl), 4-(4-hydroxy-phenyl),4-(3-fluoro-phenyl), 4-(4-fluoro-phenyl), 4-(3-chloro-phenyl),4-(4-chloro-phenyl), 4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl),4-(4-methyl-phenyl), 4-(3-trifluoromethyl-phenyl),4-(4-trifluoromethyl-phenyl), 4-(2-methoxy-phenyl),4-(3-methoxy-phenyl), 4-(4-methoxy-phenyl),4-(3-trifluoromethoxy-phenyl), 4-(4-trifluoromethoxy-phenyl),4-(3-dimethylamino-phenyl), 4-(4-dimethylamino-phenyl),4-(3-methylsulfonyl-amino-phenyl), 4-(3-amino-4-hydroxy-phenyl),4-(3-formamido-4-hydroxy-phenyl), 4-(pyridin-2-yl), 4-(pyridin-3-yl),4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl),4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl),4-(quinolin-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl),4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl),4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl),4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl),4-(benzimidazol-5-yl), 4-(benzoxazol-2-yl), 4-(benzoxazol-5-yl),4-(benzthiazol-5-yl), 4-(2,3-dimethyl-benzothiophen-5-yl),4-(1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl) and4-(1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl);

is 4-(phenyl);

and

is selected from the group consisting of 4-(4-bromo-phenyl),4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl),4-(1-methyl-pyrazol-5-yl), 4-(tetrazol-5-yl) and 3-(pyrazol-3-yl); and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl1-(ethenylcarbony)-piperidin-4,4-diyl,1-ethenylcarbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl andtetrahydro-pyran-4,4-diyl;

m is an integer from 0 to 1; and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of ethyl, 1-hydroxy-ethyl,isopropyl, 2-hydroxy-propan-2-yl, 3-hydroxy-2-methyl-propan-2-yl,2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl,1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl,1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl,1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl,oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2-yl,tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl and dimethylamino;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro,2-methyl, 2-methoxy, 3-fluoro and 3-methyl;

R⁵ is

wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl,6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl,6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl,2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl,1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl,quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl,2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl,1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl,1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl,1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl,oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl,indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl,1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl,1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl,1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl,benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl,benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl,benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl,5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl,2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl,benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl andpyrrolo[2,3-b]pyridin-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl; a is 1; L¹ is—C(O)—; R³ is selected from the group consisting of2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-methyl-cyclopropyl,pyrrolidin-1-yl and 1-methyl-pyrazol-3-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyland 2-methoxy; R⁵ is

wherein

is selected from the group consisting of 4-(4-cyano-phenyl),4-(3-hydroxy-phenyl), 4-(4-hydroxy-phenyl), 4-(3-fluoro-phenyl),4-(4-fluoro-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl),4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl), 4-(4-methyl-phenyl),4-(3-trifluoromethyl-phenyl), 4-(3-methoxy-phenyl),4-(4-methoxy-phenyl), 4-(3-dimethylamino-phenyl),4-(4-dimethylamino-phenyl), 4-(3-methylsulfonyl-amino-phenyl),4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl),4-(quinolin-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl),4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl),4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl),4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl), 4-(benzoxazol-2-yl),4-(benzoxazol-5-yl), 4-(benzthiazol-5-yl) and4-(2,3-dimethyl-benzothiophen-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl,tetrahydro-pyran-4,4-diyl;

m is an integer from 0 to 1; and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland piperidin-4-yl;

a is 1:

L¹ is —C(O)—;

R³ is selected from the group consisting of ethyl, cyclopropyl,1-hydroxy-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl,1-hydroxymethyl-cyclopropyl, cyclobutyl, tetrahydro-furan-2-yl,tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro,2-methyl, 2-methoxy, 3-fluoro and 3-methyl;

R⁵ is

wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl,2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl,indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl,1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl,2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl,2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl,quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl,1-aminoisoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl,indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl,2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl,2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl,6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl,1-(methyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyland 2-methoxy; R⁵ is

wherein

is selected from the group consisting of 4-(4-cyano-phenyl),4-(3-hydroxy-phenyl), 4-(4-fluoro-phenyl), 4-(3-chloro-phenyl),4-(4-chloro-phenyl), 4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl),4-(4-methyl-phenyl), 4-(3-methoxy-phenyl), 4-(4-methoxy-phenyl),4-(4-dimethylamino-phenyl), 4-(indol-4-yl), 4-(indol-5-yl),4-(indol-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl),4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl),4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl),4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl), 4-(benzthiazol-5-yl)and 4-(2,3-dimethyl-benzothiophen-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,tetrahydrofuran-2S-yl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro and2-methyl;

R⁵ is

wherein

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl,indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl,isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl,benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl; m is an integer from 0 to1; n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro and 2-methyl; R⁵ is

wherein

is selected from the group consisting of 4-(3-hydroxy-phenyl),4-(indol-5-yl), 4-(indol-6-yl), 4-(isoquinolin-6-yl), 4-(indazol-4-yl),4-(1-methyl-indazol-5-yl), and 4-(benzofuran-5-yl) and4-(benzthiazol-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl and cyclopentyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl,1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is selected from the group consisting of

wherein

is selected from the group consisting of naphtha-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl,indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl and1-methyl-benzimidazol-5-yl;

wherein

and wherein

is selected from the group consisting of pyridin-4-yl and1-methyl-pyrazol-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl,1-(methyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyland 1-(benzyl)-piperidin-4,4-diyl; m is an integer from 0 to 1; n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

b is an integer from 0 to 1; R⁴ is 2-methyl; R⁵ is

wherein

is selected from the group consisting of 4-(4-cyano-phenyl),4-(3-hydroxy-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl),4-(4-methyl-phenyl), 4-(4-methoxy-phenyl), 4-(indol-4-yl),4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl), 4-(isoquinolin-6-yl),4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl),4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl),4-(benzofuran-5-yl) and 4-(benzthiazol-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl and cyclopentyl; m is an integer from 0to 1; n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

wherein

is selected from the group consisting of 4-(indol-5-yl), 4-(indol-6-yl),4-(isoquinolin-6-yl) and 4-(benzofuran-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl andtetrahydropyran-4,4-diyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is selected from the group consisting of

wherein

is selected from the group consisting of naphth-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl,quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl,1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl,benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzimidazol-5-yland 1-methyl-benzimidazol-5-yl;

wherein

and wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl and pyridin-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl and cyclopentyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,1-methyl-cyclobutyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl andoxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro and2-methyl;

R⁵ is selected from the group consisting of

wherein

is selected from the group consisting of3-(cyclopropyl-sulfonylamino)-phenyl, naphth-2-yl, 6-chloro-naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl,indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 2-methyl-indol-5-yl,3-(2-hydroxyethyl)indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,8-fluoro-quinolin-2-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl,indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl,2-methyl-benzothien-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl and1-methyl-benzimidazol-5-yl;

wherein

and wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl and1-cyclobutyl-pyrazol-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form cyclopropyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is cyclopropyl;

is selected from the group consisting of

b is 0;

R⁵ is

wherein

is selected from the group consisting of indol-5-yl, indol-6-yl,indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl,benzofuran-5-yl, benzothien-5-yl and 6-cyano-naphth-2-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl, cyclopentyl, tetrahydro-furan-3,3-diyl,tetrahydro-pyran-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl,piperidin-4,4-diyl, 1-(isopropylcarbonyl)-piperidin-4,4-diyl,1-(2-hydroxyethyl)-piperidin-4,4-diyl,1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)piperidin-4,4-diyl and1-(cyclopropylcarbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 2; and n is an integer from 0 to 1; providedthat when m is 2, then n is 0;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3R-yl, piperidin-3R-yl, and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of methyl, 1-hydroxyethyl,trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl,1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl andthiazol-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is

wherein

is selected from the group consisting of phenyl, pyridin-3-yl,pyridin-4-yl and pyrazol-4-yl;

and wherein

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl,tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl,4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl, imidazol-1-yland oxetan-3-yl;

provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the binding position of the

to the

provided further that when

is pyridin-4-yl or pyrazol-4-yl, then

is bound to

at the 3-position, relative to the binding position of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl and cyclopentyl; n is an integer from 0to 1; m is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

wherein

is 4-(phenyl); and wherein

is selected from the group consisting of 4-(4-bromo-phenyl),4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl),4-(1-methyl-pyrazol-5-yl), 4-(tetrazol-5-yl), and 3-(pyrazol-3-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from thegroup consisting of cyclopropyl and cyclopentyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl,1-hydroxy-cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is

wherein

and wherein

is selected from the group consisting of 4-(pyridin-3-yl),4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl),4-(1-isopropyl-pyrazol-4-yl), 4-(1-cyclopropyl-pyrazol-4-yl),4-(1-cyclobutyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl, and4-(5-methyl-oxadiazol-2-yl);

wherein

is bound to the

phenyl at the 4-position, relative to the point of attachment of the

phenyl to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

R¹ and R² are taken together to form cyclopropyl; m is an integer from 0to 1; n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

wherein

is 4-(phenyl); and wherein

is selected from the group consisting of 4-(pyridin-3-yl) and4-(1-methyl-pyrazol-4-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form anoptionally substituted ring structure selected from the group consistingof (a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionallysubstituted with one R¹¹ group; (b) benzo-fused C₅₋₆cycloalkyl; whereinthe benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of theC₅₋₆cycloalkyl portion of the ring structure; and wherein thebenzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group;and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to8-membered, saturated heterocyclyl contains O or NR¹⁰; provided that theO or NR¹⁰ is not present at the 2-position relative to the carbon atomof the imidazolin-5-one; and wherein the 4 to 8-membered, saturatedheterocyclyl containing the O or NR¹⁰ is optionally substituted with oneR¹¹ group and further optionally substituted with one R¹² group.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form anoptionally substituted ring structure selected from the group consistingof (a) C₃₋₆cycloalkyl; and (c) 4 to 6-membered, saturated heterocyclyl;wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰;provided that the NR¹⁰ is not present at the 2-position relative to thecarbon atom of the imidazolidin-5-one.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form anoptionally substituted ring structure selected from the group consistingof (a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionallysubstituted with one R¹¹ group; (b) benzo-fused C₅₋₆cycloalkyl; whereinthe benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of theC₅₋₆cycloalkyl portion of the ring structure; and wherein thebenzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group;and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to6-membered, saturated heterocyclyl contains O or NR¹⁰; provided that theO or NR¹⁰ is not present at the 2-position relative to the carbon atomof the imidazolin-5-one; and wherein the 4 to 6-membered, saturatedheterocyclyl containing the O or NR¹⁰ is optionally substituted with oneR¹¹ group and further optionally substituted with one R¹².

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form anoptionally substituted ring structure selected from the group consistingof (a) C₃₋₆cycloalkyl; and (c) 4 to 6-membered, saturated heterocyclyl;wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰;provided that the NR¹⁰ is not present at the 2-position relative to thecarbon atom of the imidazolidin-5-one.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl, 1-(ethenyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,I-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl, and1-(methoxycarbonyl)-azetidin-3,3-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(ethenylcarbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl, andtetrahydro-pyran-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, andtetrahydro-pyran-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl,1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl,1-(isopropylcarbonyl)-piperidin-4,4-diyl,1-(2-hydroxyethyl)-piperidin-4,4-diyl,1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)piperidin-4,4-diyl, and1-(cyclopropylcarbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-cyclopropylcarbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, 1-(methyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, and1-(benzyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl,cyclopentyl, and tetrahydropyran-4,4-diyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹ and R² are taken together to form aring structure selected from the group consisting of cyclopropyl andcyclopentyl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein R¹ and R² are takentogether to form cyclopropyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹⁰ is selected from the groupconsisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxysubstituted C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B),—C(O)—(C₁₋₄alkyl), —C(O)—(C₃₋₆cycloalkyl),

wherein Z¹ is selected from the group consisting of —CH₂—, —O— and—N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independentlyselected from the group consisting of hydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹⁰ is selected from the groupconsisting of hydrogen, C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₂alkyl),—CH₂-(phenyl), —C(O)—(C₁₋₄alkyl), —C(O)-(cyclopropyl) and—C(O)—NR^(A)R^(B); wherein R^(A) and R^(B) are each independentlyselected from the group consisting of hydrogen and methyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹⁰ is selected from the groupconsisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxysubstituted C₁₋₄alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl,—(C₂alkyl)-O—(C₁₋₄alkyl), —C(O)O—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl),—C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl),

—C(O)—NR^(A)R^(B), —SO₂(C₁₋₂alkyl); wherein Z¹ is selected from thegroup consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B)and R^(C) are each independently selected from the group consisting ofhydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹⁰ is selected from the groupconsisting of hydrogen, C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxysubstituted C₁₋₂alkyl), —CH₂-(phenyl), —(C₂alkyl)-O—(C₁₋₂alkyl),—C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl),—C(O)O—(C₁₋₄alkyl), —C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl), wherein R^(A)and R^(B) are each independently selected from the group consisting ofhydrogen and methyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹¹ is independently selected from thegroup consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substitutedC₁₋₄alkyl, —(C₁₋₄ alkyl)-phenyl, -cyano, —NR^(D)R^(E),—C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄ alkyl);wherein R¹² is selected from the group consisting of hydroxy, oxo,halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substitutedC₁₋₂alkyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹² is independently selected from thegroup consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E),—C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄ alkyl).

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R¹² is selected from the groupconsisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃and hydroxy substituted CO₁₋₂alkyl. In another preferred embodiment, thepresent invention is directed to compounds of formula (I) wherein R¹² isselected from the group consisting of —OH, oxo, —Cl, —F, —CH₃, CF₃,—OCH₃, —OCF₃, —CH₂—OH and —CH₂CH₂—OH.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein m is an integer from 0 to 1; and n isan integer from 0 to 2; provided that when n is 2, then m is 0.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein m is 0. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein m is 1.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein n is 0. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein n is 1. In another preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein n is 2.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein m is 0 and n is 0. In a preferredembodiment, the present invention is directed to compounds of formula(I) wherein m is 1 and n is 1. In a preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein m is 1 and nis 0 or alternatively, m is 0 and n is 1. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein m is 0 and n is 2.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl,piperidin-3R-yl and piperidin-4-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl. In anotherpreferred embodiment the present invention is directed to compounds offormula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland piperidin-4-yl. In another preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein a is 1. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein a is 0.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein L¹ is selected from the groupconsisting of —C(O)—, —C(O)O—, —C(O)—NR^(L)— and —SO₂—; wherein R^(L) isselected from the group consisting of hydrogen and methyl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein L¹ is selected from the group consisting of —C(O)—,—C(O)O— and —SO₂—.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein L is selected from the group consistingof —C(O)—, —C(O)—NR^(L)— and —SO₂—; wherein R^(L) is selected from thegroup consisting of hydrogen and methyl. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein L¹ is selected from the group consisting of —C(O)— and—SO₂—. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein L¹ is —C(O)—.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substitutedC₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, 4 to 6-membered, saturatedheterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein R^(V)and R^(W) are each independently selected from the group consisting ofhydrogen and C₁₋₂alkyl; wherein the C₃₋₆cycloalkyl, 4 to 6-membered,saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionallysubstituted with one to two substituents independently selected from thegroup consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, —(C₁₋₂alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, andNR^(G)R^(H); wherein R^(G) and R^(H) are each independently selectedfrom the group consisting of hydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of C₁₋₄ alkyl, hydroxy substituted C₁₋₄alkyl, fluorinatedC₁₋₂alkyl, C₂₋₄alkenyl, C₃₋₅cycloalkyl, 4 to 5-membered, saturatedheterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein theC₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5 to6-membered heteroaryl is optionally substituted with a substituentselected from the group consisting of halogen, hydroxy, C₁₋₂alkyl,(C₁₋₂alkyl)-OH, fluorinated C₁₋₂alkyl, cyano and NH₂; and wherein R^(V)and R^(W) are each independently selected from the group consisting ofhydrogen and methyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of C₂₋₄alkenyl, C₃₋₆cycloalkyl, 5 to 6-membered, saturatedheterocyclyl and 5 to 6-membered heteroaryl; wherein the C₃₋₆cycloalkyl,5 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl,is optionally substituted with one to two substituents independentlyselected from the group consisting of halogen, hydroxy, cyano,C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy andNR^(G)R^(H); wherein R^(G) and R^(H) are each independently selectedfrom the group consisting of hydrogen and C₁₋₄alkyl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein R³ is selected from the group consisting ofC₂alkenyl, C₃cycloalkyl, 5-membered, saturated heterocyclyl and5-membered heteroaryl; wherein the C₃cycloalkyl, 5-membered, saturatedheterocyclyl or 5-membered heteroaryl is optionally substituted with asubstituent selected from the group consisting of halogen, C₁₋₂alkyl,fluorinated C₁₋₂alkyl and cyano.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of methyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl,2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl.3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl,1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino,dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl,tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl,3-methyl-oxetan-3-yl, and pyridin-3-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of ethyl, 1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl,3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl,cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl,1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl,cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl,oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2-yl,tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl and dimethylamino.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl and tetrahydro-furan-2-yl. Inanother preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl,1-methyl-cyclopropyl, pyrrolidin-1-yl and 1-methyl-pyrazol-3-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl,cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl,tetrahydro-furan-2S-yl, and oxetan-2-yl. In another preferredembodiment, the present invention is directed to compounds of formula(I) wherein R³ is selected from the group consisting of cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,tetrahydrofuran-2S-yl and oxetan-2-yl. In another preferred embodiment,the present invention is directed to compounds of formula (I) wherein R³is selected from the group consisting of cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl and oxetan-2-yl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein R³ is selected from the group consisting of methyl,1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl,1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl andthiazol-2-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is selected from the groupconsisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyland oxetan-2-yl. In another preferred embodiment, the present inventionis directed to compounds of formula (I) wherein R³ is selected from thegroup consisting of cyclopropyl, 1-hydroxy-cyclopropyl and1-methyl-cyclopropyl. In another preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein R³ is selectedfrom the group consisting of cyclopropyl and 1-methyl-cyclopropyl. Inanother preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R³ is cyclopropyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

One skilled in the art will recognize that in the embodiments of thepresent invention, as described herein, the

substituent group is further substituted with —(R⁴)_(b), as hereindefined.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein b is an integer from 0 to 1. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein b is 1. In another preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein b is 1

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁴ is selected from the groupconsisting of, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy and NR^(J)R^(K); wherein R^(J) and R^(K) are eachindependently selected from the group consisting of hydrogen andC₁₋₂alkyl; provided that the R⁴ group is bound to a carbon atom. Inanother preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁴ is selected from the groupconsisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁴ is selected from the groupconsisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁴ is selected from the groupconsisting of 2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyland 2-methoxy. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein R⁴ is selected from thegroup consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoroand 3-methyl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein R⁴ is selected from thegroup consisting of 2-fluoro, 2-chloro, and 2-methyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁴ is selected from the groupconsisting of 2-fluoro, 2-methyl, 3-methyl and 2-methoxy. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein R⁴ is selected from the group consisting of 2-fluoroand 2-methyl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein R⁴ is 2-methyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁵ is

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁵ is

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁵ is

and where

is a 5-membered heteroaryl, and

is bound at the 3-position, relative to the point of attachment of the

to the

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁵ is

wherein

is phenyl or a 6-membered heteroaryl, and

is bound at the 3- or 4-position, relative to the point of attachment ofthe

to the

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁵ is

wherein

is phenyl or a 6-membered heteroaryl, and

is bound at the 4-position, relative to the point of attachment of the

to the

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

selected from the group consisting of aryl, heteroaryl and partiallyunsaturated heterocyclyl. In another preferred embodiment, the presentinvention is directed to compounds of formula (I) wherein

selected from the group consisting of phenyl, heteroaryl and partiallyunsaturated heterocyclyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

selected from the group consisting of phenyl, naphthyl, 5 to 6-memberedheteroaryl, 9 to 10-membered heteroaryl and partially unsaturated 9 to10-membered heterocyclyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl,3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl,2-fluoro-4-(1-cyano-cuclopropyl)-phenyl,2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl,3-(cyclopropylcarbonyl-amino)-phenyl,3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl,3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl,3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-chloro-naphth-2-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl,6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl, 6-cyano-naphth-2-yl,7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl, 7-methoxy-naphth-2-yl,1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl,chroman-6-yl, isochroman-6-yl, isochroman-7-yl, pyridin-2-yl,pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl,6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cyclopropyl-pyridin-3-yl,6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl,5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl,1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl,1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl,1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl,quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl,quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl,2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl,2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl,2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl,2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl,2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl,3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl,4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl,2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl,2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl,3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl,6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl,3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl,3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl,quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl,1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl,1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl,1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl,1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl,2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl,1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl,1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl,1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-7-methoxymethyl-indazol-4-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-7-hydroxymethyl-indazol-4-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl,2-methyl-3-hydroxymethyl-indazol-5-yl,2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl,2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl,2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl,1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl,2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl,2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl,1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl,benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl,benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl,2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, 2,3-dihydro-benzofuran-5-yl,2-oxo-3,4-dihydro-quinolin-7-yl,1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl,1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl,2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl,pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl,[1,2,4]triazo[4,3-a]pyridin-6-yl,3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl, and4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl,6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl,6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl,2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl,1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl,quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl,2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl,1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl,1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl,1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl,oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl,indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl,1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl,1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl,1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl,benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl,benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl,benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl,5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl,2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl,benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl, andpyrrolo[2,3-b]pyridin-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl,2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl,indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl,1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl,2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl,2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl,quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl,1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl,indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl,2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl,2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl,6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,3-dimethylamino-phenyl, 4-dimethylamino-phenyl,3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl,3-formamido-4-hydroxy-phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-4-yl, indol-5-yl,indol-6-yl, quinolin-5-yl, quinolin-6-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, benzimidazol-5-yl, benzoxazol-2-yl,benzoxazol-5-yl, benzthiazol-5-yl, 2,3-dimethyl-benzothiophen-5-yl,1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, and1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl,indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl,isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl,benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl,3-methylsulfonyl-amino-phenyl, indol-4-yl, indol-5-yl, indol-6-yl,quinolin-5-yl, quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl,isoquinolin-7-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl,1-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl,benzoxazol-2-yl, benzoxazol-5-yl, benzthiazol-5-yl, and2,3-dimethyl-benzothiophen-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of naphtha-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl,indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl, and1-methy-benzimidazol-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of naphth-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl,quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl,1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl,benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl,benzimidazol-5-yl, and 1-methyl-benzimidazol-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 4-dimethylamino-phenyl, indol-4-yl, indol-5-yl,indol-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl,indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl,1-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl,benzthiazol-5-yl, and 2,3-dimethyl-benzothiophen-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of indol-5-yl, indol-6-yl,indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl,benzofuran-5-yl, benzothien-5-yl, and 6-cyano-naphth-2-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 3-hydroxy-phenyl, indol-5-yl,indol-6-yl, isoquinolin-6-yl, indazol-4-yl, 1-methyl-indazol-5-yl,benzofuran-5-yl, and benzthiazol-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl,4-methoxy-phenyl, indol-4-yl, indol-5-yl, indol-6-yl, quinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl, andbenzthiazol-5-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I wherein

is selected from the group consisting of indol-5-yl, indol-6-yl,isoquinolin-6-yl, and benzofuran-5-yl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein c is an integer from 0 to 2.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein each R⁶ is independently selected fromthe group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl,fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, cyano substituted(C₁₋₄alkyl), —(C₁₋₂alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinatedC₁₋₂alkyl), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N),—NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₅cycloalkyl,1-cyano-(C₃₋₅cycloalkyl), —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl),—S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—(C₃₋₅cycloalkyl),—NH—SO₂—(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; whereinR^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl; wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein each R⁶ is independently selected fromthe group consisting of hydroxy, oxo, halogen, cyano, C₁₋₄alkyl,fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, cyano-substitutedC₁₋₂alkyl, —(C₁₋₂alkyl)-O—(C₁₋₂alkyl), C₁₋₄alkoxy, fluorinatedC₁₋₂alkoxy, —SO₂—(C₁₋₄alkyl), —CO²H, —C(O)O—(C₁₋₂alkyl),—C(O)—(C₁₋₂alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N),—NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₂alkyl), C₃₋₅cycloalkyl,1-cyano-cyclopropyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl),—SO₂—(C₃₋₆cycloalkyl), —NH—C(O)—(C₃₋₅cycloalkyl) and—NH—SO₂—(C₃₋₅cycloalkyl), and oxetan-3-yl; and wherein R^(M) and R^(N)are each independently selected from the group consisting of hydrogenand C₁₋₂alkyl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein each R⁶ is independently selected fromthe group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl,fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy,fluorinated C₁₋₄alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₄alkyl),—C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, and—NR^(M)—SO₂—(C₁₋₄alkyl); wherein R^(M) and R^(N) are each independentlyselected from the group consisting of hydrogen and C₁₋₄alkyl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein each R⁶ is independently selected from the groupconsisting of hydroxy, halogen, cyano, C₁₋₂alkyl, fluorinated C₁₋₂alkyl,C₁₋₂alkoxy, fluorinated C₁₋₂alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₂alkyl),—NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₂alkyl); and wherein R^(M) and R^(N)are each independently selected from the group consisting of hydrogenand C₁₋₂alkyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein

is selected from the group consisting of phenyl and 6-membered, nitrogencontaining heteroaryl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of phenyl, pyridin-3-yl,pyridin-4-yl, and pyrazol-4-yl. In another preferred embodiment, thepresent invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl, pyridin-3-yl andpyridin-4-yl.

another preferred embodiment In another preferred embodiment, thepresent invention is directed to compounds of formula (I) wherein

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein d is an integer from 0 to 1.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein R⁷ is selected from the groupconsisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl,hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of phenyl, 5 to 6-memberedsaturated heterocyclyl and 5 to 6-membered heteroaryl. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein

is selected from the group consisting of phenyl, 5 to 6-membered,saturated, nitrogen containing heterocyclyl and 5 to 6-membered,nitrogen containing heteroaryl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of phenyl and 5 to 6-memberedheteroaryl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein

is selected from the group consisting of phenyl and 5 to 6-membered,nitrogen containing heteroaryl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-cyclopropyl methyl-pyrazol-3-yl,1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl,pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl,piperazin-1-yl, 4-methyl-piperazin-1-yl, and1-(oxetan-3-yl)-pyrazol-4-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein and wherein

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl,tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl,4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl,imidazol-1-yl, and oxetan-3-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl,1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl,1-methyl-pyrazol-5-yl, and 5-methyl-oxadiazol-2-yl.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl, pyridin-3-yl,pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,tetrazol-5-yl, and pyrazol-3-yl. In another preferred embodiment, thepresent invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl, pyridin-3-yl,pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,tetrazol-5-yl, and pyrazol-3-yl. In another preferred embodiment, thepresent invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and pyridin-4-yl. Inanother preferred embodiment, the present invention is directed tocompounds of formula (I) wherein

is selected from the group consisting of pyridin-3-yl and1-methyl-pyrazol-4-yl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein e is an integer from 0 to 2. In anotherpreferred embodiment, the present invention is directed to compounds offormula (I) wherein e is an integer from 0 to 1.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein each R⁸ is independently selected fromthe group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinatedC₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH,—C(O)O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl,—(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; whereinR^(T) and R^(U) are each independently selected from the groupconsisting of hydrogen and C₁₋₄alkyl. In another preferred embodiment,the present invention is directed to compounds of formula (I) wherein R⁸is selected from the group consisting of halogen, C₁₋₄alkyl,C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), and oxetanyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) wherein each R⁸ is independently selected fromthe group consisting of hydroxy, halogen, cyano, C₁₋₄ alkyl, fluorinatedC₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinatedC₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and —(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are eachindependently selected from the group consisting of hydrogen andC₁₋₄alkyl. In another preferred embodiment, the present invention isdirected to compounds of formula (I) wherein R⁸ is selected from thegroup consisting of halogen and C₁₋₂alkyl.

In a preferred embodiment, the present invention is directed tocompounds of formula (I) selected from the group consisting of5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one;6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-(4-(6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;5-(4-(benzo[d]thiazol-2-yl)-2-fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one,and stereoisomers, tautomers, and pharmaceutically acceptable saltsthereof.

In another preferred embodiment, the present invention is directed tocompounds of formula (I) selected from the group consisting of6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;and stereoisomers, tautomers and pharmaceutically acceptable saltsthereof.

In an embodiment, the present invention is directed to compounds offormula (I) wherein R¹ and R² are taken together with the carbon atom towhich they are bound to form a ring structure other thantetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl.

In an embodiment, the present invention is directed to compounds offormula (I) wherein (L¹)_(a) is other than —SO₂-pyrrolidin-1-yl or—SO₂-pyridin-3-yl. In another embodiment, the present invention isdirected to compounds of formula (I) wherein (L¹)_(a) is other thanC(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ or —SO₂—CH₃.

In an embodiment, the present invention is directed to compounds offormula (I) wherein R⁵ is other than1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl),1,2,3,4-trihydro-2-methylcarbonyisoquinolin-2-yl,4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl,2-oxo-3,4-dihydro-quinolin-7-yl, 5-chloro-pyridin-3-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl,6-(1-cyanomethyl)-pyridin-3-yl,6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl,2-(piperazin-1-yl)-pyridin-4-yl,2-(4-methyl-piperazin-1-yl)-pyridin-4-yl,6-(morpholin-4-yl)-pyridin-3-yl, 1,5-naphthyridin-3-yl,3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, or6-(4-methyl-piperazin-1-yl)-pyridin-3-yl.

In an embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to form1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and—SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl,1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl,4-(1-methyl-pyrazol-4-yl)-phenyl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl,2-(piperazin-1-yl)-pyridin-4-yl or2-(4-methyl-piperazin-1-yl)-pyridin-4-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl,1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl,indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl,6-(1-cyanomethyl)-pyridin-3-yl,6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl,3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl,4-(l-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is—C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl,benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or4-(3-chlorophenyl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other 4-trifluoromethylphenyl,1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl,2-oxo-3,4-dihydro-quinolin-7-yl, or6-(4-methyl-piperazin-1-yl)pyridin-3-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formtetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integerfrom 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland pyrrolidin-3-yl; (L¹)_(a)-R³ is selected from the group consistingof —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl,benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to form1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is1;

is pyrrolidin-3R-yl; -(L¹)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, or1-methyl-indazol-5 yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)), is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R is other than benzoxazol-5-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R is other than 2-oxo-3,4-dihydro-quinolin-7-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to form1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is1;

is pyrrolidin-3R-yl; -(L¹)-R³ is selected from the group consisting of—C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and—SO₂—CH₃;

and b=0: then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than2-(piperazin-1-yl)-pyridin-4-yl or2-(4-methyl-piperazin-1-yl)-pyridin-4-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0, and

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 4-(1-isobutyl-pyrazol-5-yl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 2,

is piperidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(4-methylphenyl)phenyl or4-(3-chlorophenyl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1, and

is piperidin-4-yl; -(L¹)_(a)-R is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl.

In another embodiment, the present invention is directed to compounds offormula (I) as herein described, provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to formtetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integerfrom 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from thegroup consisting of —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

Additional embodiments of the present invention, include those whereinthe substituents selected for one or more of the variables definedherein (e.g. R¹, R², R³, R⁴, R⁵, L¹, a, b, m, n,

etc.) are independently selected to be any individual substituent or anysubset of substituents selected from the complete list as definedherein.

In additional embodiments, the present invention is directed to anysingle compound or subset of compounds, selected from the representativecompounds listed in Tables 1-4, below.

Representative compounds of formula (I) of the present invention arelisted in Table 1 to 4, below. Unless otherwise noted, where astereogenic center is present in the listed compound, the compound wasprepared as a mixture of stereo-configurations. Where a stereogeniccenter is present, the S- and R-designations are intended to indicatethat the exact stereo-configuration of the center has been determined.

As used herein, for example, as in the Tables below, the “R¹ & R² takentogether” substituent group is named independent of the imidazolid-5-onecore with which it forms a spiro-ring system, with the two of thespiro-bond positions denoted in the name. For example, wherein R¹ and R²are taken together with the carbon atom to which they are bound to forma spiro-ring of the following structure:

the substituent group “R¹ & R² taken together” is named/denoted as1-(methoxy-carbonyl)-piperidin-4,4-diyl; wherein the “4,4-diyl”nomenclature indicating that the two bonds creating the spiro linkageare made through the 4-position on the piperidine portion of thespiro-ring structure.

TABLE 1 Representative Compounds of Formula (I)

                      ID No.                   R¹ & R² taken together

                      (L¹)_(a)                       R³                      (R⁴)_(b)              

 1 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-cyano-phenyl 3R-yl 2 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl 3 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-4-yl 3R-yl  4cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl  5cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-3-yl 3R-yl  6cyclopropyl piperidin- C(O) cyclopropyl b = 0 pyridin-3-yl 4-yl  7cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-cyano-phenyl 4-yl  8cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-ylpyrazol-5-yl  9 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl-4-yl pyrazol-4-yl  10 cyclopropyl piperidin- C(O) cyclopropyl b = 0indol-5-yl 4-yl  11 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0quinolin-6-yl 3R-yl  12 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-6-yl 3R-yl  13 cyclopentyl pyrrolidin- C(O) cyclopropyl b =0 1-methyl- 3R-yl pyrazol-4-yl  14 1-(methoxy- pyrrolidin- C(O)cyclopropyl b = 0 benzofuran-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 15 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)-3R-yl piperidin- 4,4-diyl  16 1-(methoxy- azetidin-3- C(O) cyclopropyl b= 0 benzofuran-5-yl carbonyl)- yl piperidin- 4,4-diyl  17 1-(methoxy-azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)- yl piperidin-4,4-diyl  18 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-2-yl3R-yl  19 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-ylindazol-5-yl  20 cyclopropyl piperidin- C(O) cyclopropyl b = 0isoquinolin-6-yl 4-yl  22 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0quinolin-4-yl 3R-yl  24 cyclopropyl piperidin- C(O) cyclopropyl b = 01-methyl- 4-yl indazol-6-yl  25 cyclopropyl piperidin- C(O) cyclopropylb = 0 isoquinolin-7-yl 4-yl  26 cyclopropyl piperidin- C(O) cyclopropylb = 0 benzimidazol-5- 4-yl yl  27 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-methyl- 3R-yl indazol-6-yl  28 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-5-yl  29cyclopropyl piperidin- C(O) cyclopropyl b = 0 indazol-5-yl 4-yl  30cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-7-yl 3R-yl 31 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl  32cyclopropyl piperidin- C(O) cyclopropyl b = 0 pyridin-4-yl 4-yl  33cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indol-6-yl 3R-yl  34cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-ylindazol-6-yl  35 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 01-methyl- 3R-yl indazozl-5-yl  36 cyclopentyl pyrrolidin- C(O)cyclopropyl b = 0 benzoxazol-2-yl 3R-yl  37 cyclopropyl piperidin- C(O)cyclopropyl b = 0 benzoxazol-5-yl 4-yl  38 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-methyl- yl indazol-6-yl  39 cyclopropyl azetidin-3-C(O) cyclopropyl b = 0 1-methyl- yl indazol-5-yl  40 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 indol-5-yl yl  41 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 4-cyano-phenyl yl  42 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl pyrazol-4-yl  43cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- ylpyreazol-5-yl  47 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-6-yl 3R-yl  48 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 4-cyano-phenyl 3R-yl  49 cyclopropyl azetidin-3- C(O) cyclopropyl b =0 benzofuran-5-yl yl  50 cyclopropyl azetidin-3- C(O) cyclopropyl b = 04-hydroxy- yl phenyl  51 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0indazol-5-yl yl  52 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0benzoxazol-5-yl yl  53 cyclopropyl azetidin-3- C(O) cyclopropyl b = 03-amino-4- yl hydroxy-phenyl  54 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 3-form-amido-4- yl hydroxy-phenyl  55 cyclopropylpiperidin- C(O) cyclopropyl b = 0 4-hydroxy- 4-yl phenyl  57 cyclopropylpiperidin- C(O) cyclopropyl b = 0 benzothiazol-5- 4-yl yl  58cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl  631-(benzyl)- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl piperidin-3R-yl 4,4-diyl  64 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 04-hydroxy- 3R-yl phenyl  66 cyclopentyl pyrrolidin- C(O) cyclopropyl b =0 quinolin-5-yl 3R-yl  67 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-5-yl 3R-yl  68 cyclopentyl pyrrolidin- C(O) cyclopropyl b =0 indol-4-yl 3R-yl  69 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-7-yl 3R-yl  71 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 benzothiazol-5- 3R-yl yl  72 cyclopentyl pyrrolidin- C(O) cyclopropyl2- benzofuran-5-yl 3R-yl methyl  73 cyclopentyl pyrrolidin- C(O)cyclopropyl 2- indol-5-yl 3R-yl methyl  74 cyclopentyl pyrrolidin- C(O)cyclopropyl 2- isoquinolin-6-yl 3R-yl methyl  75 cyclopentyl piperidin-C(O) cyclopropyl b = 0 benzofuran-5-yl 4-yl  76 cyclopentyl piperidin-C(O) cyclopropyl b = 0 indol-5-yl 4-yl  77 cyclopentyl piperidin- C(O)cyclopropyl b = 0 isoquinolin-6-yl 4-yl  78 cyclopentyl azetidin-3- C(O)cyclopropyl b = 0 indol-5-yl yl  79 cyclopentyl azetidin-3- C(O)cyclopropyl b = 0 isoquinolin-6-yl yl  80 cyclopentyl azetidin-3- C(O)cyclopropyl b = 0 benzofuran-5-yl yl  81 1-methyl- pyrrolidin- C(O)cyclopropyl b = 0 indol-5-yl piperidin- 3R-yl 4,4-diyl  82 cyclopentylpyrrolidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 3R-yl  83 cyclopentylpyrrolidin- C(O) cyclopropyl b = 0 3-cyano-phenyl 3R-yl  84 cyclopentylpyrrolidin- C(O) cyclopropyl b = 0 3-methyl- 3R-yl sulfonyl-amino-phenyl  85 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-methoxy-3R-yl phenyl  90 1-(benzyl)- pyrrolidin- C(O) ethenyl b = 0benzofuran-5-yl piperidin- 3R-yl 4,4-diyl)  92 cyclopentyl pyrrolidin-C(O) cyclopropyl b = 0 indazol-4-yl 3R-yl  93 cyclopentyl pyrrolidin-C(O) cyclopropyl 2- 4-chloro-phenyl 3R-yl methyl  94 cyclopentylpyrrolidin- C(O) cyclopropyl 2- 2,4-dichloro- 3R-yl methyl phenyl  951-(benzyl)- pyrrolidin- C(O) NH₂ b = 0 benzofuran-3-yl piperidin- 3R-yl4,4-diyl)  96 1-(benzyl)- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl piperidin- 3R-yl 4,4-diyl)  97 cyclopropyl piperidin-C(O) cyclopropyl b = 0 4-methyl-phenyl 4-yl  98 cyclopropyl piperidin-C(O) cyclopropyl b = 0 2-methoxy- 4-yl phenyl  99 cyclopropyl piperidin-C(O) cyclopropyl b = 0 4-methoxy- 4-yl phenyl 100 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 4-methyl-phenyl 3R-yl 101 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-methyl-phenyl 3R-yl 102 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-fluoro-phenyl) 3R-yl 103cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-methoxy- 3R-yl phenyl104 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-trifluoro- 3R-ylmethyl-phenyl 105 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 04-fluoro-phenyl) 3R-yl 106 piperidin- pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-6-yl 4,4-yl 3R-yl 107 cyclopropyl piperidin- C(O)cyclopropyl b = 0 4-trifluoro- 4-yl methyl-phenyl 108 cyclopropylpiperidin- C(O) cyclopropyl b = 0 3-hydroxy- 4-yl phenyl 109 cyclopropylpiperidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 4-yl 110 cyclopropylpiperidin- C(O) cyclopropyl b = 0 4-fluoro-phenyl 4-yl 111 cyclopropylpiperidin- C(O) cyclopropyl b = 0 3-methyl-phenyl 4-yl 112 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-chloro-phenyl 3R-yl 113 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-methoxy- 3R-yl phenyl 114cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 3R-yl 115cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-hydroxy- 3R-yl phenyl116 cyclopentyl pyrrolidin- C(O) 1-methyl- b = 0 benzofuran-5-yl 3R-ylcycloprop- 1-yl 117 cyclopentyl pyrrolidin- C(O) pyrrolidin- b = 0benzofuran-5-yl 3S-yl 1-yl 118 cyclopentyl pyrrolidin- C(O) 1-methyl- b= 0 benzofuran-5-yl 3R-yl pyrazol-3-yl 119 cyclopentyl pyrrolidin- C(O)2,2,2- b = 0 benzofuran-5-yl 3R-yl trifluoro- ethyl 120 cyclopentylpyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl fluoro 121cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-chloro-phenyl 3R-yl fluoro123 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-cyano-phenyl 3R-yl124 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-dimethyl- 3R-ylamino-phenyl 125 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 04-trifluoro- 3R-yl methoxy-phenyl 126 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 3-trifluoro- 3R-yl methyl-phenyl 127 1-(2- pyrrolidin-C(O) cyclopropyl b = 0 1-methyl- hydroxy- 3R-yl indazol-5-yl ethyl)-piperidin- 4,4-diyl 128 piperidin- pyrrolidin- C(O) cyclopropyl b = 01-methyl- 4,4-diyl 3R-yl indazol-5-yl 129 1- azetidin-3- C(O)cyclopropyl b = 0 benzofuran-5-yl (isopropyl- yl carbonyl)- piperidin-4,4-yl 130 piperidin- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl4,4-diyl yl 131 piperidin- azetidin-3- C(O) cyclopropyl b = 0 1-methyl-4,4-diyl yl indazol-5-yl 132 piperidin- azetidin-3- C(O) cyclopropyl b =0 isoquinolin-6-yl 4,4-diyl yl 133 piperidin- pyrrolidin- C(O)cyclopropyl b = 0 benzofuran-5-yl 4,4-diyl 3R-yl 134 1- azetidin-3- C(O)cyclopropyl b = 0 benzofuran-5-yl (cyclopropyl- yl carbonyl)- piperidin-4,4-diyl 135 1- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- (isopropyl-yl indazol-5-yl carbonyl)- piperidin- 4,4-diyl 136 1-(dimethyl-azetidin-3- C(O) cyclopropyl b = 0 1-methyl- amino- yl indazol-5-ylmethyl- carbonyl)- piepridin- 4,4-diyl 137 1- azetidin-3- C(O)cyclopropyl b = 0 isoquinolin-6-yl (isopropyl- yl carbonyl)- piperidin-4,4-diyl 138 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-carbonyl)- 3R-yl indazol-5-yl piperidin- 4,4-yl 139 1- pyrrolidin- C(O)cyclopropyl b = 0 1-methyl- (isopropyl- 3R-yl indazol-5-yl carbonyl)-piperidin- 4,4-diyl 140 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyk-(cyclopropyl- 3R-yl indazol-5-yl carbonyl)- piperidin- 4,4-yl 1411-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- amino- 3R-ylindazol-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 142 1-(dimethyl-pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl amino- 3R-yl methyl-carbonyl)- piperidin- 4,4-diyl 143 1- pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-6-yl (isopropyl- 3R-yl carbonyl)- piperidin- 4,4-diyl 1441-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-ylcarbonyl)- 3R-yl piperidin- 4,4-diyl 145 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 3-dimethyl- 3R-yl amino-phenyl 146 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-trifluoro- 3R-yl methoxy-phenyl 1471-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)-3R-yl piperidin- 4,4-diyl 148 1-(methyl- pyrrolidin- C(O) cyclopropyl b= 0 indazol-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 149 1-(dimethyl-azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl amino- yl methyl-carbonyl)- piperidin- 4,4-diyl 150 1-(methyl- pyrrolidin- C(O)cyclopropyl b = 0 benzofuran-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl151 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl-3R-yl carbonyl)- piperidin- 4,4-diyl 152 1- pyrrolidin- C(O) cyclopropylb = 0 benzofuran-5-yl (cyclopropyl- 3R-yl carbonyl)- piperidin- 4,4-diyl153 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-ylamino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 154 1-(dimethyl-azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl amino- yl methyl-carbonyl)- piperidin- 4,4-diyl 155 piperidin- pyrrolidin- C(O)cyclopropyl b = 0 2-methyl- 4,4-diyl 3R-yl benzofuran-5-yl 156cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl meth-oxy 157 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-ylmeth- oxy 158 cyclopropyl piperidin- C(O) cyclopropyl b = 03-fluoro-phenyl 4-yl 159 1-(2- pyrrolidin- C(O) cyclopropyl b = 0isoquinolin-6-yl hydroxy- 3R-yl ethyl)- piperidin- 4,4-diyl 1601-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 1,2,3,4-trihydro-carbonyl)- 3R-yl 2-methyl- piperidin- carbonyl- 4,4-diylisoquinolin-6-yl 161 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 01,2,3,4,4a,8a- carbonyl)- 3R-yl hexahydro-2- piperidin- methyl- 4,4-diylcarbonyl- isoquinolin-6-yl 162 1- pyrrolidin- C(O) cyclopropyl b = 01-methyl- (isopropyl)- 3R-yl indazol-5-yl piperidin- 4,4-diyl 163 1-pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl (isopropyl)- 3R-ylpiperidin- 4,4-diyl 164 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0indol-5-yl amino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 1651-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl amino-3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 166 1- azetidin-3- C(O)cyclopropyl b = 0 benzofuran-5-yl (isopropyl)- yl piperidin- 4,4-diyl167 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl)-3R-yl piperidin- 4,4-yl 168 1-(2- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl hydroxy- 3R-yl ethyl)- piperidin- 4,4-diyl 169 1-azetidin-3- C(O) cyclopropyl b = 0 1-methyl- (isopropyl)- ylindazol-5-yl piperidin- 4,4-diyl 170 1-(2- azetidin-3- C(O) cyclopropylb = 0 1-methyl- hydroxy- yl indazol-5-yl ethyl)- piperidin- 4,4-diyl 1711- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- (cyclopropyl- 3R-ylbenzofuran-5-yl carbonyl)- piperidin- 4,4-diyl 172 1- pyrrolidin- C(O)cyclopropyl b = 0 2-methyl- (isopropyl- 3R-yl benzofuran-5-yl carbonyl)-piperidin- 4,4-diyl 173 1-(2- pyrrolidin- C(O) cyclopropyl b = 02-methyl- hydroxy- 3R-yl benzofuran-5-yl ethyl)- piperidin- 4,4-diyl 1741-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- amino- 3R-ylbenzofuran-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 178 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl benzofuran-5-yl 179cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl methylbenzofuran-5-yl 180 cyclopropyl pyrrolidin- C(O) cyclopropyl 3-benzofuran-5-yl 3R-yl methyl 181 1-(methyl- pyrrolidin- C(O) cyclopropylb = 0 2,3-dimethyl- carbonyl)- 3R-yl benzothien-5-yl piperidin- 4,4-diyl182 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- amino-3R-yl benzothien-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 183 1-pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- (isopropyl- 3R-ylbenzothien-5-yl carbonyl)- piperidin- 4,4-diyl 184 1- pyrrolidin- C(O)cyclopropyl b = 0 2,3-dimethyl- (isopropyl)- 3R-yl benzothien-5-ylpiperidin- 4,4-diyl 185 1-(2- azetidin-3- C(O) cyclopropyl b = 0benzofuran-5-yl hydroxy- yl ethyl)- piperidin- 4,4-diyl 186 1-pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- (isopropyl)- 3R-ylbenzofuran-5-yl piperidin- 4,4-diyl 187 1- azetidin-3- C(O) cyclopropylb = 0 indol-5-yl (isopropyl)- yl piperidin- 4,4-diyl 188 1- azetidin-3-C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl)- yl piperidin- 4,4-diyl189 cyclopentyl pyrrolidin- SO₂ pyrrolidin- b = 0 benzofuran-5-yl 3S-yl1-yl 190 cyclopentyl pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl3R-yl furan-2S-yl 191 cyclopentyl pyrrolidin- C(O) tetrahydro- b = 0benzofuran-5-yl 3R-yl furan-2R-yl 192 cyclopentyl pyrrolidin- C(O)1-cyano- b = 0 benzofuran-5-yl 3R-yl cyclopropyl 193 1-(benzyl)-pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl piperidin- 3R-yl4,4-diyl) 200 cyclopropyl pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl-3R-yl cyclopropyl indazol-5-yl 201 cyclopropyl pyrrolidin- C(O)1-methyl- b = 0 1-methyl- 3R-yl cyclopropyl indazol-5-yl 202 cyclopropylpyrrolidin- C(O) 1-hydroxy- b = 0 2-fluoro-4- 3R-yl cyclopropylchloro-phenyl 203 cyclopropyl pyrrolidin- C(O) 1-hydroxy- b = 06-methoxy- 3R-yl cyclopropyl naphth-2-yl 204 cyclopropyl pyrrolidin-C(O) oxetan-2-yl b = 0 1-methyl- 3R-yl indazol-5-yl 205 cyclopropylazetidin-3- C(O) tetrahydro- 2- 1-methyl- yl furan-2-yl methylindazol-5-yl 206 cyclopropyl azetidin-3- C(O) tetrahydro- 2- 1-methyl-yl furan-2S-yl methyl indazol-5-yl 207 cyclopropyl azetidin-3- C(O)1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 208cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclobutyl methylindazol-5-yl 209 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 03-chloro-4- 3R-yl fluoro-phenyl 210 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 indol-5-yl 3S-yl 211 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 benzothien-5-yl 3S-yl 212 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 3-cyanomethyl- 3R-yl indol-5-yl 213 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl indol-5-yl 214cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-methyl-indol- 3R-yl5-yl 215 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-indol-3R-yl 5-yl 216 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-hydroxy-3R-yl methyl-indol-5- yl 217 cyclopropyl pyrrolidin- C(O) cyclopropyl b= 0 3-(2- 3R-yl hydroxyethyl)- indol-5-yl 218 cyclopropyl pyrrolidin-C(O) cyclopropyl b = 0 1,3-dimethyl- 3R-yl indazol-5-yl 219 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-amino- 3R-yl isoquinolin-6-yl 220cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-fluoro- 3R-ylisoquinolin-6-yl 221 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 01-methyl-3- 3R-yl aminocarbonyl- indazol-6-yl 222 cyclopropylazetidin-3- C(O) cyclopropyl 2- 6-cyano-naphth- yl fluoro 2-yl 223cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-fluoro-naphth- yl methyl2-yl 224 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-cyano-naphth- ylmethyl 2-yl 225 cyclopropyl azetidin-3- C(O) 1-fluoro- 2-6-cyano-naphth- yl cyclopropyl fluoro 2-yl 226 cyclopropyl azetidin-3-C(O) oxetan-2-yl 2- 6-cyano-naphth- yl fluoro 2-yl 227 cyclopropylazetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro indazol-6-yl 228cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-fluoro- yl fluoroquinolin-2-yl 229 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-cyano-3R-yl fluoro quinolin-6-yl 230 cyclopropyl pyrrolidin- C(O) cyclopropyl2- benzothien-5-yl 3R-yl methyl 231 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- 2,3-dimethyl- 3R-yl methyl benzothien-5-yl 232cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl fluoro233 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-ylfluoro 234 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-ylfluoro 236 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-ylfluoro 237 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-4-yl3R-yl fluoro 238 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl3R-yl fluoro 239 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl3R-yl methyl 240 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-benzofuran-5-yl 3R-yl fluoro 241 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- benzothien-5-yl 3R-yl fluoro 242 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- 2-methyl- 3R-yl fluoro benzofuran-5-yl 243cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl fluorobenzothien-5-yl 244 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-2,3-dimethyl- 3R-yl fluoro benzofuran-5-yl 245 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl fluoro benzothien-5-yl 246cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl fluoro 247cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl fluoro 248cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-6-yl 3R-yl fluoro249 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-7-yl 3R-ylfluoro 250 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-5-yl3R-yl fluoro 251 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-benzoxazol-2-yl 3R-yl fluoro 252 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- benzthiazol-2-yl 3R-yl fluoro 253 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- indazol-5-yl 3R-yl fluoro 254 cyclopropylpyrrolidin- C(O) cyclopropyl 2- 2-cyano- 3R-yl fluoro benzofuran-5-yl255 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-cyano- 3R-yl methylbenzofuran-5-yl 256 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 02-cyano- 3R-yl benzofuran-5-yl 257 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- quinolin-3-yl 3R-yl fluoro 258 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- quinazolin-7-yl 3R-yl fluoro 259 cyclopropylpyrrolidin- C(O) cyclopropyl 2- 6-fluoro- 3R-yl fluoro quinolin-2-yl 260cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 8-fluoro- 3R-yl fluoroquinolin-2-yl 261 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-3-yl3R-yl fluoro 262 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 1-mehtyl-3R-yl methyl indazol-5-yl 263 cyclopropyl azetidin-3- C(O) cyclopropyl2- 2-methyl-indol- yl methyl 5-yl 264 cyclopropyl azetidin-3- C(O)1-hydroxy- 2- 1-methyl- yl cyclopropyl chloro indazol-5-yl 265cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 1-methyl- 3R-yl cyclopropylmethyl indazol-5-yl 266 cyclopropyl pyrrolidin- C(O) 1-methyl- 2-6-fluoro-naphth- 3R-yl cycloprropyl methyl 2-yl 268 cyclopropylazetidin-3- C(O) cyclopropyl 2- 6-cyano- yl fluoro benzthiazol-2-yl 269cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-cyano-naphth- yl cyclopropylmethyl 2-yl 270 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-methyl- ylfluoro benzthiazol-2-yl 271 cyclopropyl azetidin-3- C(O) cyclopropyl 2-6-fluoro- yl fluoro benzthiazol-2-yl 272 cyclopropyl azetidin-3- C(O)1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl methyl 2-yl 273 cyclopropylazetidin-3- C(O) 1-fluoro- 2- 6-cyano-naphth- yl cyclopropyl methyl 2-yl274 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-chloro- yl fluorobenzthiazol-2-yl 275 cyclopropyl azetidin-3- C(O) cyclopropyl b = 06-fluoro- yl quinolin-2-yl 276 cyclopropyl azetidin-3- C(O) cyclopropylb = 0 2-cyano- yl quinolin-6-yl 277 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 6-cyano- yl quinolin-2-yl 278 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl methyl 279 cyclopropylpyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl methyl 280cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl methylbenzofuran-5-yl 281 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-2-methyl- 3R-yl methyl benzothien-5-yl 282 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- 2,3-dimethyl- 3R-yl methyl benzofuran-5-yl 283cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl methylbenzothien-5-yl 284 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-indol-5-yl 3R-yl methyl 286 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-indazol-5-yl 3R-yl methyl 287 cyclopropyl azetidin-3- C(O) cyclopropyl2- benzofuran-5-yl yl methyl 288 cyclopropyl azetidin-3- C(O)cyclopropyl 2- benzothien-5-yl yl methyl 289 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 2-methyl- yl methyl benzofuran-5-yl 290 cyclopropylazetidin-3- C(O) cyclopropyl 2- 2,3-dimethyl- yl methyl benzothien-5-yl291 cyclopropyl azetidin-3- C(O) cyclopropyl 2- indol-5-yl yl methyl 292cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl methylindazol-5-yl 293 cyclopropyl azetidin-3- C(O) cyclopropyl 2-indazol-5-yl yl methyl 294 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 2-methyl- 3R-yl benzofuran-5-yl 295 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 2-methyl- 3R-yl benzothien-5-yl 296 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl benzothien-5-yl297 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl 3R-yl298 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benothien-5-yl 3R-yl299 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indol-6-yl yl 300cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indazol-4-yl yl 301cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-6-yl 3R-yl 302cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-4-yl 3R-yl 303cyclopropyl azetidin-3- C(O) cyclopropyl 2- indol-6-yl yl methyl 304cyclopropyl azetidin-3- C(O) cyclopropyl 2- indazol-4-yl yl methyl 305cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl methyl 306cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-4-yl 3R-yl methyl307 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzoxazol-2-yl 3R-yl308 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzthiazol-2-yl3R-yl 309 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl3R-yl 310 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-5-yl3R-yl 311 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 06-fluoro-naphth- 3R-yl 2-yl 312 cyclopropyl pyrrolidin- C(O) cyclopropylb = 0 quinazolin-7-yl 3R-yl 313 cyclopropyl pyrrolidin- C(O) cyclopropylb = 0 8-fluoro-naphth- 3R-yl 2-yl 314 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 indol-3-yl 3R-yl 315 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 8-fluoro- yl quinolin-7-yl 317 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- 2-methyl-indol- 3R-yl methyl 5-yl 318 cyclopropylpyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluorosulfonyl-amino)- phenyl 319 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-2-methyl-indol- 3R-yl fluoro 5-yl 320 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 6-chloro- yl fluoro naphth-2-yl 321 cyclopropylazetidin-3- C(O) 1-methyl- 2- 6-chloro- yl cyclopropyl methylnaphth-2-yl 324 cyclopropyl azetidin-3- C(O) cyclopropyl 2-7-fluoro-naphth- yl fluoro 2-yl 332 cyclopropyl azetidin-3- C(O)1-methyl- 2- 6-methoxy- yl cyclopropyl methyl naphth-2-yl 334cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-methyl- yl cyclopropylmethyl naphth-2-yl 335 cyclopropyl azetidin-3- C(O) 1-methyl- 2-1-methyl- yl cyclopropyl methyl indazol-6-yl 336 cyclopropyl azetidin-3-C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl methyl indazol-6-yl 339cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-chloro- ylquinolin-7-yl 340 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 3-chloro- ylcyclopropyl methyl quinolin-7-yl 343 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-methyl- yl benzimidazol-5- yl 344 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 1-methyl-indol- yl 5-yl 345cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinolin-2-yl yl 346cyclopropyl azetidin-3- C(O) cyclopropyl 2- quinolin-7-yl yl fluoro 347cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl fluoroindazol-5-yl 348 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-yl fluoro benzimidazol-5- yl 349 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 6-fluoro-naphth- yl fluoro 2-yl 350 cyclopropylazetidin-3- C(O) cyclopropyl 2- 8-fluoro-naphth- yl fluoro 2-yl 351cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-methoxy- yl fluoronaphth-2-yl 352 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- ylcyclopropyl fluoro benzothien-5-yl 353 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 2-methyl- yl fluoro benzofuran-5-yl 354 cyclopropylpyrrolidin- C(O) 1-hydroxy- 2- 2-methyl- 3R-yl cyclopropyl fluorobenzothien-5-yl 355 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 2-methyl-3R-yl cyclopropyl fluoro benzofuran-5-yl 356 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 2-methyl- yl fluoro benzothiazol-5- yl 357cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropylfluoro indazol-5-yl 359 cyclopropyl azetidin-3- C(O) 1-methyl- 2-6-fluoro-naphth- yl cyclopropyl fluoro 2-yl 361 cyclopropyl pyrrolidin-C(O) 1-methyl- 2- 1-methyl- 3R-yl cyclopropyl fluoro indazol-5-yl 363cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 6-fluoro-naphth- 3R-ylcyclopropyl fluoro 2-yl 365 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2-6-fluoro-naphth- yl cyclopropyl fluoro 2-yl 366 cyclopropyl azetidin-3-C(O) 1-hydroxy- 2- 6-methoxy- yl cyclopropyl fluoro naphth-2-yl 368cyclopropyl azetidin-3- C(O) cyclopropyl 2- naphth-2-yl yl fluoro 369cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-fluoro-naphth- yl fluoro2-yl 370 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 1-methyl- 3R-ylcyclopropyl fluoro indazol-5-yl 372 cyclopropyl azetidin-3- C(O)1-hydroxy- 2- naphth-2-yl yl cyclopropyl fluoro 373 cyclopropylazetidin-3- C(O) 1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl fluoro2-yl 374 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 8-fluoro-naphth- ylcyclopropyl fluoro 2-yl 375 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2-8-methoxy- yl cyclopropyl fluoro naphth-2-yl 377 cyclopropyl azetidin-3-C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl fluoro benzimidazol-5- yl378 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropylfluoro benzimidazol-5- yl 380 cyclopropyl azetidin-3- C(O) cyclopropyl2- 8-methoxy- yl fluoro naphth-2-yl 381 cyclopropyl pyrrolidin- C(O)1-hydroxy- 2- 6-fluoro-naphth- 3R-yl cyclopropyl fluoro 2-yl 383cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-chloro- yl cyclopropylfluoro naphth-2-yl 384 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2-7-fluoro-naphth- yl cyclopropyl fluoro 2-yl 385 cyclopropyl azetidin-3-C(O) 1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl fluoro 2-yl 387cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl- 3R-yl fluorobenzofuran-5-yl 388 cyclopropyl pyrrolidin- C(O) cyclopropyl 3-2-methyl- 3R-yl methyl benzofuran-5-yl 389 cyclopropyl piperidin- C(O)cyclopropyl b = 0 indazol-5-yl 3R-yl 391 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 2-methyl- yl methyl benzothien-5-yl 392 cyclopropylazetidin-3- C(O) cyclopropyl 3- benzothien-5-yl yl methyl 393cyclopropyl azetidin-3- C(O) cyclopropyl 3- benzofuran-5-yl yl methyl394 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3R-yl395 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl396 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3R-ylindazol-5-yl 398 cyclopropyl azetidin-3- C(O) cyclopropyl 2-2,3-dimethyl- yl methyl benzofuran-5-yl 399 cyclopropyl pyrrolidin- C(O)cyclopropyl 3- 2,3-dimethyl- 3R-yl fluoro benzofuran-5-yl 400cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 6-amino-pyridin- 3R-yl2-yl 401 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-methoxy- 3R-ylcarbonyl-phenyl 404 cyclopropyl azetidin-3- C(O) cyclopropyl 3-benzothien-5-yl yl fluoro 405 cyclopropyl pyrrolidin- C(O) cyclopropyl3- 1-methyl- 3R-yl fluoro indazol-5-yl 406 cyclopropyl pyrrolidin- C(O)cyclopropyl 3- 2,3-dimethyl- 3R-yl fluoro benzothien-5-yl 408cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-hydroxy- 3S-yl phenyl409 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl410 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3S-ylindazol-5-yl 414 cyclopropyl pyrrolidin- C(O) cyclopropyl 3-indazol-5-yl 3R-yl fluoro 415 cyclopropyl azetidin-3- C(O) cyclopropyl3- benzofuran-5-yl yl fluoro 416 cyclopropyl azetidin-3- C(O)cyclopropyl 3- 2-methyl- yl fluoro benzofuran-5-yl 417 cyclopropylazetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl fluoro benzofuran-5-yl418 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2,3-dimethyl- ylbenzothien-5-yl 431 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0indazol-5-yl 3S-yl 432 cyclopropyl azetidin-3- C(O) cyclopropyl b = 02-methyl- yl benzothien-5-yl 433 cyclopropyl azetidin-3- C(O)cyclopropyl 3- 2-methyl- yl fluoro benzothien-5-yl 434 cyclopropylazetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl fluoro benzothien-5-yl435 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-yl yl methyl 436cyclopropyl azetidin-3- C(O) cyclopropyl 3- 1-methyl- yl methylindazol-5-yl 440 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-ylyl fluoro 441 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 1-methyl- ylfluoro indazol-5-yl 442 cyclopropyl azetidin-3- C(O) cyclopropyl 3-indol-6-yl yl fluoro 443 cyclopropyl azetidin-3- C(O) cyclopropyl 3-indazol-4-yl yl fluoro 444 cyclopropyl pyrrolidin- C(O) cyclopropyl 3-indazol-5-yl 3R-yl methyl 445 cyclopropyl pyrrolidin- C(O) cyclopropyl3- indazol-4-yl 3R-yl methyl 446 cyclopropyl azetidin-3- C(O)cyclopropyl 3- 2-methyl- yl methyl benzothien-5-yl 447 cyclopropylazetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl methyl benzothien-5-yl448 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indazol-5-yl yl methyl449 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-yl yl methyl 450cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 1-methyl- 3R-yl methylindazol-5-yl 451 cyclopropyl azetidin-3- C(O) cyclopropyl 3-indazol-5-yl yl fluoro 452 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 2-amino-pyridin- 3R-yl 4-yl 453 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 isochroman-7-yl 3R-yl 454 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-isopropyl- 3R-yl indazol-5-yl 455 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 quinolin-6-yl 3R-yl 456 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 2,3-dihydro- 3R-yl benzo[1,4]dioxin-6-yl 457 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-indolin-5-3R-yl yl 460 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-cyano- ylmethyl benzofuran-5-yl 461 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 2-oxo-indolin-5- 3R-yl yl 462 cyclopropyl pyrrolidin- C(O) cyclopropylb = 0 2,3-dihydro- 3R-yl benzofuran-5-yl 463 cyclopropyl pyrrolidin-C(O) cyclopropyl 3- 2-cyano- 3R-yl fluoro benzofuran-5-yl 464cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 chroman-6-yl 3R-yl 465cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-ylcyclopropyl- indazol-5-yl 466 cyclopropyl pyrrolidin- C(O) cyclopropyl b= 0 3-chloro- 3R-yl isoquinolin-6-yl 467 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-oxo- 3R-yl isoquinolin-6-yl 468 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 1-methoxy- 3R-yl isoquinolin-6-yl 469cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-amino- 3R-ylisoquinolin-6-yl 470 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 03-methoxy- 3R-yl isoquinolin-6-yl 471 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 isochroman-6-yl 3R-yl 472 cyclopropyl azetidin-3- C(O)ethyl 2- 1-methyl- yl methyl indazol-5-yl 473 cyclopropyl azetidin-3-C(O) isopropyl 2- 1-methyl- yl methyl indazol-5-yl 474 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 quinolin-3-yl 3R-yl 475 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2-cyano- yl benzofuran-5-yl 476cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-cyano- 3R-yl methylbenzofuran-5-yl 477 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-cyano-yl fluoro benzofuran-5-yl 478 cyclopropyl pyrrolidin- C(O) cyclopropyl b= 0 6-bromo- 3R-yl isoquinolin-3-yl 479 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-chloro- 3R-yl isoquinolin-6-yl 480 cyclopropylazetidin-3- C(O) 1- 2- 1-methyl- yl hydroxy- methyl indazol-5-yl methyl-cyclopropyl 481 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0quinoxalin-6-yl yl 483 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 01-methyl-3- 3R-yl amino-indazol- 6-yl 484 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-methyl-3- 3R-yl methoxymethyl- indazol-6-yl 485cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-ylhydroxymethyl- indazol-6-yl 486 cyclopropyl pyrrolidin- C(O) cyclopropylb = 0 1-methyl-7- 3R-yl methoxymethyl- indazol-4-yl 487 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 1-methyl-7- 3R-yl hydroxymethyl-indazol-5-yl 488 cyclopropyl azetidin-3- C(O) dimethylamino 2- 1-methyl-yl methyl indazol-5-yl 489 cyclopropyl azetidin-3- C(O) cyclobutyl 2-1-methyl- yl methyl indazol-5-yl 490 cyclopropyl pyrrolidin- C(O)oxetan-3-yl b = 0 1-methyl- 3R-yl indazol-5-yl 491 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 1,4-dimethyl- yl indazol-5-yl 492cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,7-dimethyl- ylindazol-5-yl 493 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 01-methyl-3- 3R-yl cyano-indazol- 6-yl 494 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 3-amino- 3R-yl carbonyl-phenyl 495 cyclopropylazetidin-3- C(O) 2-hydroxy- 2- 1-methyl- yl propan-2-yl methylindazol-5-yl 496 cyclopropyl azetidin-3- C(O) 3-methyl- 2- 1-methyl- yloxetan-3-yl methyl indazol-5-yl 497 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 benzimidazol-2- 3R-yl yl 498 cyclopropyl azetidin-3-C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 499cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl methylindazol-5-yl 500 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 01,2-dimethyl- 3R-yl 1,2-dihydro-3- oxo-indazol-5-yl 501 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2- yl cyclopropyl-methyl-indazol-5-yl 502 cyclopropyl azetidin-3- C(O) cyclopropyl b = 03-fluoro- yl isoquinolin-6-yl 503 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-mehtyl- yl pyrazolo[3,4- b]pyridin-5-yl 504cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 benzoisoxazol-5- yl yl505 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-ethyl-indazol- yl5-yl 506 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-ethyl-indazol-yl 5-yl 507 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- ylindazol-5-yl 508 cyclopropyl azetidin-3- C(O) cyclopropyl b = 01-isopropyl- yl indol-5-yl 510 cyclopropyl azetidin-3- C(O) cyclopropylb = 0 2-methyl- yl quinolin-6-yl 511 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1,8- yl naphthyridin-2- yl 512 cyclopropyl pyrrolidin-C(O) cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro- quinolin-6-yl 513cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- ylquinolin-7-yl 515 cyclopropyl azetidin-3- C(O) cyclopropyl b = 01-methyl- yl indazol-4-yl 518 cyclopropyl azetidin-3- C(O) thiazol-2-yl2- 1-methyl- yl methyl indazol-5-yl 519 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 quinolin-3-yl yl 520 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 1,8-dimethyl- yl fluoro indazol-5-yl 521 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-ethyl-indazol- yl fluoro 5-yl 522cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-cyclopropyl- yl fluoroindazol-5-yl 523 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1- ylfluoro cyclopropyl- methyl-indazol-5-yl 524 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 2- yl fluoro cyclopropyl- methyl-indazol-5-yl 525cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-isopropyl- yl fluoroindazol-5-yl 527 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-(2- ylfluoro hydroxyethyl)- indazol-5-yl 528 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 indazol-3-yl 3R-yl 529 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- indazol-3-yl 3R-yl fluoro 530 cyclopropyl azetidin-3-C(O) cyclopropyl b = 0 1-methyl-3- yl hydroxymethyl- indazol-5-yl 531cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-3-yl yl 532cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-hydroxy- ylquinolin-3-yl 533 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-(2-yl cyanoethyl)- indazol-5-yl 535 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 2-methyl-4- yl chloro-quinolin- 7-yl 536 cyclopropylazetidin-3- C(O) cyclopropyl 2- 2-(2- yl fluoro hydroxyethyl)-indazol-5-yl 537 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-fluoro-4-yl fluoro chloro-phenyl 538 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-benzimidazol-2- 3R-yl fluoro yl 539 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1,2,4- yl triazolo[4,3- 1]pyridin-6-yl 540 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2-chloro- yl quinolin-7-yl 541cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl-indol- yl 6-yl543 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinazolin-7-yl yl545 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 1-methyl- yl methylindazol-5-yl 546 cyclopropyl azetidin-3- C(O) 3-hydroxy- 2- 1-methyl- yl2-methyl- methyl indazol-5-yl propan-2-yl 548 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 2-methyl- yl fluoro benzothien-5-yl 549 cyclopropylb = 0 2-(2- azetidin-3- C(O) cyclopropyl hydroxyethyl)- yl indazol-5-yl550 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-isopropyl- ylindazol-5-yl 551 cyclopropyl azetidin-3- C(O) cyclopropyl b = 02-isopropyl- yl indazol-5-yl 552 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-(2- yl hydroxyethyl)-6- fluoro-indazol-5- yl 553cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-(2- yl hydroxyethyl)-6-fluoro-indazol-5- yl 554 cyclopropyl azetidin-3- C(O) cyclopropyl b = 04-methyl- yl quinolin-7-yl 555 cyclopropyl azetidin-3- C(O) cyclopropylb = 0 2-chloro-3- yl methyl-quinolin- 7-yl 556 cyclopropyl azetidin-3-C(O) cyclopropyl b = 0 1-(2- yl hydroxyethyl)- indazol-5-yl 557cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-ylmethoxy- indazol-5-yl 558 cyclopropyl azetidin-3- C(O) cyclopropyl 2-2-methyl- yl fluoro benzothiazol-6- yl 559 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 2-chloro-4- yl methyl-quinolin- 7-yl 560 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 8-fluoro- yl quinolin-2-yl 561cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl-8- ylfluoro-quinolin- 7-yl 562 cyclopropyl azetidin-3- C(O) cyclopropyl b = 02-methyl- yl benzothiazol-5- yl 563 cyclopropyl azetidin-3- C(O)cyclopropyl 4-chloro- yl quinolin-7-yl 564 cyclopropyl azetidin-3- C(O)1-amino- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 568 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-methyl-3-(2- yl fluoro hydroxyethyl)-indol-5-yl 569 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,2-dimethyl-yl fluoro indol-5-yl 570 cyclopropyl azetidin-3- C(O) cyclopropyl b = 02,4-dimethyl- yl quinolin-7-yl 571 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 3-(cyclopropyl- yl methyl carbonyl- amino)-phenyl 572cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropylfluoro indazol-5-yl 573 cyclopropyl azetidin-3- C(O) cyclopropyl 2-1,3-dimethyl- yl fluoro indol-5-yl 574 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 2-methyl- yl fluoro quinolin-7-yl 575 cyclopropylazetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro quinolin-5-yl 576cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropylmethyl quinolin-7-yl 578 cyclopropyl azetidin-3- C(O) cyclopropyl 2-2-(cyclopropyl- yl methyl sulfonyl-amino)- phenyl 579 cyclopropylazetidin-3- C(O) 1-methyl- 2- 2- yl cyclopropyl methyl aminocarbonyl-quinolin-7-yl 580 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-fluoro-4-yl cyclopropyl methyl cyano-phenyl 581 cyclopropyl azetidin-3- C(O)1-methyl- 2- 6-isopropyloxy- yl cyclopropyl methyl naphthyl-2-yl 582cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,2-dimethyl- yl methylindol-5-yl 583 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-carboxy-yl quinolin-7-yl 584 cyclopropyl azetidin-3- C(O) cyclopropyl 2-1-methyl- yl chloro indazol-5-yl 585 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluoro carbonyl- amino)-phenyl 586cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methylhydroxymethyl- indazol-5-yl 587 cyclopropyl azetidin-3- C(O) cyclopropyl2- 2-methyl-3- yl methyl hydroxymethyl- indazol-5-yl 588 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl methoxymethyl-indazol-5-yl 589 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-3-yl methyl methoxymethyl- indazol-5-yl 590 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 1-methyl-3- yl methyl chloro-indazol- 6-yl 591cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methylchloro-indazol- 5-yl 592 cyclopropyl azetidin-3- C(O) cyclopropyl 2-4-chloro- yl fluoro indazol-5-yl 593 cyclopropyl azetidin-3- C(O)1-methyl- 2- 2-fluoro-4-(1- yl cyclopropyl methyl cyano- cyclopropyl)-phenyl 594 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro- ylcyclopropyl methyl quinolin-7-yl 595 cyclopropyl azetidin-3- C(O)1-methyl- 2- 7-bromo- yl cyclopropyl methyl quinolin-2-yl 596cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro-3- yl cyclopropylmethyl methyl-quinolin- 7-yl 597 cyclopropyl azetidin-3- C(O) 1-methyl-2- 2-methyl-4- yl cyclopropyl methyl chloro-quinolin- 7-yl 598cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropylmethyl indazol-4-yl 599 cyclopropyl azetidin-3- C(O) 1-methyl- 2-1-methyl- yl cyclopropyl methyl indazol-4-yl 600 cyclopropyl azetidin-3-C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-3-yl 603cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropylmethyl quinolin-5-yl 604 cyclopropyl azetidin-3- C(O) 1-methyl- 2-2-cyano- yl cyclopropyl methyl quinolin-7-yl 605 cyclopropyl azetidin-3-C(O) 1-methyl- 2- 4-methyl-7- yl cyclopropyl methyl beomo-quinolin- 2-yl606 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluorochloro-indazol- 6-yl 607 cyclopropyl azetidin-3- C(O) cyclopropyl 2-1-methyl-3- yl fluoro choro-indazol- 5-yl 608 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 1-methyl-3- yl fluoro methoxymethyl- indazol-5-yl609 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluorohydroxymethyl- indazol-5-yl 610 cyclopropyl azetidin-3- C(O) cyclopropyl2- 2-methyl-3- yl methyl cyano-indazol- 5-yl 611 cyclopropyl azetidin-3-C(O) cyclopropyl b = 0 2-cyano- yl quinolin-7-yl 612 cyclopropylazetidin-3- C(O) cyclopropyl 3- 1-methyl- yl chloro indazol-5-yl 613cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl methylsulfonyl-amino)- phenyl 614 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-3-(cyclopropyl- 3R-yl methyl carbonyl- amino)-phenyl 615 cyclopropylazetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl fluoro carbonyl-amino)-phenyl 616 cyclopropyl azetidin-3- C(O) cyclopropyl 2-7-cyano-methyl- yl fluoro 2-yl 617 cyclopropyl azetidin-3- C(O)1-hydroxy- 2- 7-methoxy- yl cyclopropyl fluoro naphth-2-yl 618cyclopropyl azetidin-3- C(O) cyclopropyl 2- 7-methoxy- yl fluoronaphth-2-yl 619 cyclopropyl azetidin-3- C(O) cyclopropyl 2-3-(cyclopropyl- yl fluoro carbonyl- amino)-phenyl 620 cyclopropylazetidin-3- C(O) 1-methyl- 2- 2- yl cyclopropyl methyl trifluoromethyl-quinolin-7-yl 621 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2-7-cyano-naphth- yl cyclopropyl fluoro 2-yl 622 cyclopropyl azetidin-3-C(O) 1-hydroxy- 3- 1-mehtyl- yl cyclopropyl chloro indazol-5-yl 624cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro-4- yl cyclopropylmethyl methyl-quinolin- 7-yl 627 cyclopropyl azetidin-3- C(O) 1-methyl-2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 628 cyclopropylazetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methylindazol-5-yl 629 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 4-chloro-yl methyl indazol-6-yl 630 cyclopropyl azetidin-3- C(O) cyclopropyl 2-2-fluoro-5- yl fluoro trifluoromethyl- phenyl 631 cyclopropylazetidin-3- C(O) cyclopropyl 2- 3-(isopropyl- yl fluoro sulfonyl)-phenyl632 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(isopropyl- 3R-ylfluoro sulfonyl)-phenyl 633 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-3-(methyl- 3R-yl methyl sulfonyl)-phenyl 634 cyclopropyl pyrrolidin-C(O) cyclopropyl 2- 3-(methyl- 3R-yl fluoro sulfonyl)-phenyl 635cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-methoxy- yl fluoronaphth-2-yl 636 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-3-(isopropyl- 3R-yl methyl sulfonyl)-phenyl 637 cyclopropyl azetidin-3-C(O) 1-fluoro- 2- 1-methyl- yl cyclopropyl fluoro indazol-5-yl 638cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-fluoro- yl fluorobenzothiazol-2- yl 639 cyclopropyl azetidin-3- C(O) cyclopropyl 2-5,6-difluoro- yl fluoro benzothiazol-2- yl 640 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 3-(cyclopropyl- yl methyl sulfonyl)-phenyl 641cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluorothio)-phenyl 642 cyclopropyl pyrrolidin- C(O) cyclopropyl 2-3-(cyclopropyl- 3R-yl methyl thio)-phenyl 643 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 5-chloro- yl fluoro benzothiazol-2- yl 644cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoroindazol-5-yl 645 cyclopropyl azetidin-3- C(O) cyclopropyl 2-3-(cyclopropyl- yl fluoro thio)-phenyl 646 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- 3-(cyclopropyl- 3R-yl methyl sulfonyl)-phenyl 647cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluorosulfonyl)-phenyl 648 cyclopropyl azetidin-3- C(O) cyclopropyl 2-1-methyl- yl fluoro benzimidazol-2- yl 649 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 6-chloro- yl fluoro benzoxazol-2-yl 650 cyclopropylazetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl methylsulfonyl)-phenyl 651 cyclopropyl azetidin-3- C(O) cyclopropyl 2-3-(cyclopropyl- yl fluoro sulfonyl)-phenyl 652 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 5-cy7ano- yl fluoro benzothiazol-2- yl 653cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-6- yl fluorofluoro- benzimidazol-2- yl 654 cyclopropyl azetidin-3- C(O) cyclopropyl2- 1,2-dimethyl- yl fluoro benzimidazol-6- yl 661 tetrahydro-pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl pyran-4,4- 3R-yl diyl662 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 quinolin-7-ylpyran-4,4- 3R-yl ethyl diyl 663 tetrahydro- pyrrolidin- C(O) tetrahydro-b = 0 quinolin-7-yl pyran-4,4- 3R-yl furan-2R-yl diyl 664 tetrahydro-pyrrolidin- C(O)O methyl b = 0 quinolin-7-yl pyran-4,4- 3R-yl diyl 665tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl pyran-4,4-3R-yl 1-yl diyl 666 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0quinolin-7-yl pyran-4,4- 3R-yl diyl 667 tetrahydro- pyrrolidin- C(O)cyclopropyl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 668 tetrahydro-pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl pyran-4,4- 3R-yl ethyldiyl 669 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-ylpyran-4,4- 3R-yl furan-2R-yl diyl 670 tetrahydro- pyrrolidin- C(O)trifluoromethyl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 671tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-ylpyran-4,4- 3S-yl 1-yl diyl 672 tetrahydro- pyrrolidin- C(O) cyclopropylb = 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 673 tetrahydro-pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- pyran-4,4- 3R-yl ethylindazol-5-yl diyl 674 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 01-methyl- pyran-4,4- 3R-yl furan-2R-yl indazol-5-yl diyl 675 tetrahydro-pyrrolidin- C(O) pyrrolidin- b = 0 1-methyl- pyran-4,4- 3S-yl 1-ylindazol-5-yl diyl 680 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0quinolin-7-yl furan-3,3- 3R-yl diyl 681 tetrahydro- pyrrolidin- C(O)1-hydroxy- b = 0 quinolin-7-yl furan-3,3- 3R-yl ethyl diyl 682tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 quinolin-7-yl furan-3,3-3R-yl furan-2R-yl diyl 683 tetrahydro- pyrrolidin- C(O)O methyl b = 0quinolin-7-yl furan-3,3- 3S-yl diyl 684 tetrahydro- pyrrolidin- C(O)trifluoromethyl b = 0 quinolin-7-yl furan-3,3- 3R-yl diyl 685tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl furan-3,3-3S-yl 1-yl diyl 686 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl furan-3,3- 3R-yl diyl 687 tetrahydro- pyrrolidin- C(O)1-hydroxy- b = 0 benzofuran-5-yl furan-3,3- 3R-yl ethyl diyl 688tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-ylfuran-3,3- 3R-yl furan-2R-yl diyl 689 tetrahydro- pyrrolidin- C(O)pyrrolidin- b = 0 benzofuran-5-yl furan-3,3- 3S-yl 1-yl diyl 690tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- furan-3,3-3R-yl indazol-5-yl diyl 691 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b =0 1-methyl- furan-3,3- 3R-yl ethyl- indazol-5-yl diyl 692 tetrahydro-pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- furan-3,3- 3R-ylfuran-2R-yl indazol-5-yl diyl 693 tetrahydro- pyrrolidin- C(O)pyrrolidin- b = 0 1-methyl- furan-3,3- 3S-yl 1-yl indazol-5-yl diyl 698tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 quinolin-7-yl pyran-4,4-yl diyl 699 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 quinolin-7-ylpyran-4,4- yl ethyl diyl 700 tetrahydro- azetidin-3- C(O) tetrahydro- b= 0 quinolin-7-yl pyran-4,4- yl furan-2R-yl diyl 701 tetrahydro-azetidin-3- C(O) pyrrolidin- b = 0 quinolin-7-yl pyran-4,4- yl 1-yl diyl702 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-ylpyran-4,4- yl diyl 703 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0benzofuran-5-yl pyran-4,4- yl ethyl diyl 704 tetrahydro- azetidin-3-C(O) tetrahydro- b = 0 benzofuran-5-yl pyran-4,4- yl furan-2R-yl diyl705 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 benzofuran-5-ylpyran-4,4- yl 1-yl diyl 706 tetrahydro- azetidin-3- C(O) cyclopropyl b =0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 707 tetrahydro- azetidin-3-C(O) 1-hydroxy- b = 0 1-methyl- pyran-4,4- yl ethyl indazol-5-yl diyl708 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 1-methyl- pyran-4,4-yl furan-2R-yl indazol-5-yl diyl 709 tetrahydro- azetidin-3- C(O)pyrrolidin- b = 0 1-methyl- pyran-4,4- yl 1-yl indazol-5-yl diyl 714tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 quinolin-7-yl furan-3,3-yl diyl 715 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 quinolin-7-ylfuran-3,3- yl ethyl diyl 716 tetrahydro- azetidin-3- C(O) tetrahydro- b= 0 quinolin-7-yl furan-3,3- yl furan-2R-yl diyl 717 tetrahydro-azetidin-3- C(O) pyrrolidin- b = 0 quinolin-7-yl furan-3,3- yl 1-yl diyl718 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-ylfuran-3,3- yl diyl 719 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0benzofuran-5-yl furan-3,3- yl ethyl diyl 720 tetrahydro- azetidin-3-C(O) tetrahydro- b = 0 benzofuran-5-yl furan-3,3- yl furan-2R-yl diyl721 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 benzofuran-5-ylfuran-3,3- yl 1-yl diyl 722 tetrahydro- azetidin-3- C(O) cyclopropyl b =0 1-methyl- furan-3,3- yl indazol-5-yl diyl 723 tetrahydro- azetidin-3-C(O) 1-hydroxy- b = 0 1-methyl- furan-3,3- yl ethyl indazol-5-yl diyl724 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 1-methyl- furan-3,3-yl furan-2R-yl indazol-5-yl diyl 728 1-(methoxy- pyrrolidin- C(O)cyclopropyl b = 0 quinolin-7-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 7291-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 quinolin-7-yl carbonyl)-3R-yl ethyl azetidin- 3,3-diyl 730 1-(methoxy- pyrrolidin- C(O)tetrahydro- b = 0 quinolin-7-yl carbonyl)- 3R-yl furan-2R-yl azetidin-3,3-diyl 731 1-(methoxy- pyrrolidin- C(O) trifluoromethyl b = 0quinolin-7-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 732 1-(methoxy-pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl carbonyl)- 3R-yl 1-ylazetidin- 3,3-diyl 733 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 734 1-(methoxy-pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl carbonyl)- 3R-yl ethylazetidin- 3,3-diyl 735 1-(methoxy- pyrrolidin- C(O) tetrahydro- b = 0benzofuran-5-yl carbonyl)- 3R-yl furan-2R-yl azetidin- 3,3-diyl 7361-(methoxy- pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-ylcarbonyl)- 3S-yl 1-yl azetidin- 3,3-diyl 737 1-(methoxy- pyrrolidin-C(O) cyclopropyl b = 0 1-methyl- carbonyl)- 3R-yl indazol-5-yl azetidin-3,3-diyl 738 1-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl-carbonyl)- 3R-yl ethyl indazol-5-yl azetidin- 3,3-diyl 739 1-(methoxy-pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- carbonyl)- 3R-ylfuran-2R-yl indazol-5-yl azetidin- 3,3-diyl 740 1-(methoxy- pyrrolidin-C(O) pyrrolidin- b = 0 1-methyl- carbonyl)- 3S-yl 1-yl indazol-5-ylazetidin- 3,3-diyl 741 1-(ethenyl- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-6-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 742 1-(2-pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- hydroxy- 3R-ylbenzothien-5-yl ethyl)- piperidin- 4,4-diyl 743 1- pyrrolidin- C(O)cyclopropyl b = 0 indazol-5-yl (isopropyl)- 3R-yl piperidin- 4,4-yl 7441- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl)- 3R-ylpiperidin- 4,4-diyl 745 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0indazol-5-yl sulfonyl)- 3R-yl piperidin- 4,4-diyl 746 1-(methyl-pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl sulfonyl)- 3R-ylpiperidin- 4,4-yl 747 1-(2- pyrrolidin- C(O) cyclopropyl b = 0indol-5-yl (methoxy) 3R-yl ethyl)- piperidin- 4,4-diyl 748 1-(2-pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl (methoxy) 3R-yl ethyl)-piperidin- 4,4-diyl 749 1-(2- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl (methoxy) 3R-yl ethyl)- piperidin- 4,4-diyl 750 1-(2-pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (methoxy) 3R-ylindazol-5-yl ethyl)- piperidin- 4,4-diyl 751 1- pyrrolidin- C(O)cyclopropyl b = 0 indol-5-yl (trifluoro- 3R-yl methyl)- carbonyl)-piperidin- 4,4-diyl 752 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-(trifluoro- 3R-yl indazol-5-yl methyl)- carbonyl)- piperidin- 4,4-diyl753 1- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl (isopropyl- ylcarbonyl)- piperidin- 4,4-diyl 754 1- azetidin-3- C(O) cyclopropyl b = 0indazol-5-yl (isopropyl- yl carbonyl)- piperidin- 4,4-diyl 755 1-(2-azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl (methoxy) yl ethyl)-piperidin- 4,4-diyl 756 1-(2- azetidin-3- C(O) cyclopropyl b = 0indazol-5-yl (methoxy- yl ethyl)- piperidin- 4,4-diyl 757 1-(2-azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl hydroxy- yl ethyl)-piperidin- 4,4-diyl 758 1-(2- azetidin-3- C(O) cyclopropyl b = 0indazol-5-yl hydroxy- yl ethyl)- piperidin- 4,4-diyl 760 1-(methyl-azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl sulfonyl)- ylpiperidin- 4,4-diyl 761 1-(methyl- azetidin-3- C(O) cyclopropyl b = 01-methyl- sulfonyl)- yl indazol-5-yl piperidin- 4,4-diyl 762 1-(methyl-azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl sulfonyl)- yl piperidin-4,4-diyl 763 1-(methyl- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-ylsulfonyl)- yl piperidin- 4,4-diyl 764 1- azetidin-3- C(O) cyclopropyl b= 0 benzofuran-5-yl (trifluoro- yl methyl- carbonyl)- piperidin-4,4-diyl 765 1- azetidin-3- C(O) cyclopropyl indol-5-yl (trifluoro- ylmethyl- carbonyl)- piperidin- 4,4-diyl 766 1- azetidin-3- C(O)cyclopropyl b = 0 indazol-5-yl (trifluoro- yl methyl- carbonyl)-piperidin- 4,4-diyl 775 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-yl methyl methylsulfonyl- phenyl 776 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 3- yl methyl isopropylsulfonyl- phenyl 777 cyclopropylazetidin-3- C(O) cyclopropyl 2- 3- yl fluoro methylsulfonyl- phenyl 784cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-isopropyl- ylpyridin-3-yl 787 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 3-methyl-7-yl cyclopropyl methyl bromo-quinolin- 2-yl 788 cyclopropyl azetidin-3-C(O) cyclopropyl b = 0 1-oxetan-3-yl- yl indazol-5-yl 789 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-oxetan-3-yl- yl fluoro indazol-5-yl790 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- ylquinolin-5-yl 791 cyclopropyl azetidin-3- C(O) cyclopropyl b = 04-methyl-7- yl bromo-quinolin- 2-yl 792 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-methyl-1H- yl pyrazolo[4,3- b]pyridin-5-yl 793cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-methyl- yl[1,2,4]triazolo[4, 3-a]pyridin-6-yl 794 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 5-(2-hydroxy-2- yl methyl-propyl)- pyrid-2-yl 795cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-n-propyl- ylpyridin-3-yl 796 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- ylcyclopropyl methyl indazol-5-yl 797 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 6-(2-hydroxy-2- yl methyl-propyl)- pyridin-3-yl 798cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-chyclopropyl- ylpyridin-3-yl 799 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,,8- ylnaphthyridin-3- yl 800 cyclopropyl azetidin-3- C(O) cyclopropyl b = 06-(1-cyano- yl cyclopropyl)- pyrid-3-yl 801 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1,5- yl naphthyridin-3- yl 802 cyclopropyl pyrrolidin-C(O) cyclopropyl b = 0 5-chloro-pyridin- 3R-yl 3-yl 803 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 1-cyclopropyl- yl indazol-5-yl 804cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1- yl cycloprropyl-methyl-indazol-3-yl 805 cyclopropyl azetidin-3- C(O) pyridin-3-yl 2-1-methyl- yl methyl indazol-5-yl 807 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-isopropyl- yl indazol-5-yl 808 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2-isopropyl- yl indazol-5-yl 809cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro-quinolin-7-yl 811 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 02-isopropyl- 3R-yl indazol-5-yl 814 cyclopropyl azetidin-3- C(O)cyclopropyl 3- 2,3-dimethyl- yl methyl benzofu-5-yl 816 cyclopropylpiperidin- C(O) cyclopropyl b = 0 indazol-5-yl 3S-yl 817 cyclopropylpiperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3S-yl 818 cyclopropylpiperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl 819 cyclopropylpiperidin- C(O) cyclopropyl b = 0 1-methyl- 3S-yl indazol-5-yl 822cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-methyl-3,4- 3R-yl methyldihydro-2H- pyrido[3,2- b][1,4]oxazin-7- yl 834 cyclopropyl azetidin-3-C(O) cyclopropyl 2- 1-methyl-3- yl fluoro cyano-indazol- 5-yl 836cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methylcyano-indazol- 5-yl 837 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-(2-yl cyclopropyl fluoro hydroxyethyl)- indazol-5-yl 839 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 2-methyl-7- yl bromo-quinolin- 2-yl840 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-oxo-quinolin- yl7-yl 841 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 7-bromo- ylquinolin-2-yl 842 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-(2-yl cyanoethyl)- indazol-5-yl 843 cyclopropyl piperidin- C(O) cyclopropylb = 0 indol-5-yl 3S-yl 844 cyclopropyl pyrrolidin- C(O) cyclopropyl b =0 1-methyl- 3R-yl indazol-5-yl 845 cyclopropyl pyrrolidin- C(O)cyclopropyl 2- indol-5-yl 3R-yl fluoro 846 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 2,3-dimethyl- yl benzofuran-5-yl 847 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl benzofuran-5-yl848 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3- 3R-ylcarboxyphenyl 849 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl-3R-yl methyl benzothien-5-yl 850 cyclopropyl pyrrolidin- C(O)cyclopropyl 3- 2-methyl- 3R-yl fluoro benzothien-5-yl 851 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl 855 cyclopentylpyrrolidin- C(O) cyclopropyl 2- 5-chloro-pyridin- 3R-yl methyl 3-yl 859cyclopropyl piperidin- C(O) cyclopropyl b = 0 4- 4-yl trifluoromethyl-phenyl 867 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 05-amino-pyridin- 3R-yl 3-yl 868 cyclopropyl azetidin-3- C(O) cyclopropyl2- benzothiazol-2- yl fluoro yl 869 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 2-methyl-indol- yl fluoro 5-yl 870 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-methyl-indol- yl fluoro 5-yl 871cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 1-methyl- 3R-yl fluoroindazol-5-yl 872 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2-6-cyano-methyl- yl cyclopropyl fluoro 2-yl 873 cyclopentyl pyrrolidin-C(O) cyclopropyl 2- indol-6-yl 3R-yl methyl 874 cyclopentyl pyrrolidin-C(O) cyclopropyl 2- indol-6-yl 3R-yl fluoro 875 cyclopentyl pyrrolidin-C(O) cyclopropyl 2- quinolin-7-yl 3R-yl fluoro 876 cyclopentylpyrrolidin- C(O) cyclopropyl 2- benzothien-7-yl 3R-yl fluoro 877cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzimidazol-5- 3R-yl fluoroyl 878 cyclopentyl pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl3R-yl cyclopropyl 879 cyclopentyl pyrrolidin- C(O) cyclopropyl 2-indazol-6-yl 3R-yl fluoro 880 cyclopentyl pyrrolidin- C(O) cyclopropyl2- 1-methyl- 3R-yl fluoro indazol-5-yl 881 cyclopentyl pyrrolidin- C(O)cyclopropyl 2- pyrrolo[2,3- 3R-yl fluoro b]pyridin-5-yl 883 cyclopentylpyrrolidin- C(O) cyclopropyl 2- benzo[1,3]dioxol- 3R-yl methyl 5-yl 884cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 2,3- 3R-yl methyldihydrobenzo- furan-5-yl 885 cyclopentyl pyrrolidin- C(O) cyclopropyl 2-2-oxo- 3R-yl fluoro benzimidazol-5- yl 886 cyclopentyl pyrrolidin- C(O)cyclopropyl 2- 4- 3R-yl fluoro (methylcarbonyl)- phenyl 887 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 5-bromo- yl pyridin-2-yl 888tetrahydro- azetidin-3- SO₂ methyl b = 0 benzofuran-5-yl pyran-4,4- yldiyl 889 tetrahydro- pyrrolidin- C(O)O methyl b = 0 benzofuran-5-ylpyran-4,4- 3S-yl diyl 890 tetrahydro- pyrrolidin- C(O) trifluoromethyl b= 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 892 tetrahydro-pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3- 3R-ylindazol-5-yl diyl 895 tetrahydro- azetidin-3- C(O) trifluoromethyl b = 0quinolin-7-yl furan-3,3- yl diyl 896 tetrahydro- pyrrolidin- SO₂ methylb = 0 quinolin-7-yl furan-3,3- 3-yl diyl 897 tetrahydro- azetidin-3-C(O) trifluoromethyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 898tetrahydro- azetidin-3- SO₂ methyl b = 0 benzofuran-5-yl furan-3,3- yldiyl 900 1- pyrrolidin- SO₂ methyl b = 0 quinolin-7-yl methoxycar- 3S-ylbonyl)- azetidin- 3,3-diyl 902 tetrahydro- azetidin-3- SO₂ methyl b = 01-methyl- pyran-4,4- yl indazol-5-yl diyl 903 tetrahydro- azetidin-3-C(O)O methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 904 tetrahydro-azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 905tetrahydro- azetidin-3- C(O)O methyl b = 0 1-methyl- furan-3,3- ylindazol-5-yl diyl 907 1- pyrrolidin- C(O) trifluoromethyl b = 01-methyl- methoxycar- 3R-yl indazol-5-yl bonyl)- azetidin- 3,3-diyl 908tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- ylindazol-5-yl diyl 909 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 01-methyl- furan-3,3- yl indazol-5-yl diyl 910 tetrahydro- azetidin-3-C(O) trifluoromethyl b = 0 quinolin-7-yl pyran-4,4- yl diyl 912tetrahydro- azetidin-3- SO₂ methyl b = 0 quinolin-7-yl pyran-4,4- yldiyl 913 tetrahydro- pyrrolidin- SO₂ methyl b = 0 benzofuran-5-ylpyran-4,4- 3S-yl diyl 914 tetrahydro- pyrrolidin- SO₂ methyl b = 0benzofuran-5-yl furan-3,3- 3S-yl diyl 915 tetrahydro- pyrrolidin- C(O)Omethyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 916 1-pyrrolidin- C(O)O methyl b = 0 1-methyl- methoxycar- 3S-yl indazol-5-ylbonyl)- azetidin- 3,3-diyl 917 1- pyrrolidin- SO₂ methyl b = 0 1-methyl-methoxycar- 3S-yl indazol-5-yl bonyl)- azetidin- 3,3-diyl 920tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 quinolin-7-yl furan-3,3-3R-yl diyl 922 tetrahydro- azetidin-3- C(O)O methyl b = 0 quinolin-7-ylpyran-4,4- yl diyl 923 1- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl-methoxycar- 3R-yl indazol-5-yl bonyl)- azetidin- 3,3-diyl 925cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-hydroxy- 3R-yl phenyl926 tetrahydro- pyrrolidin- SO₂ methyl b = 0 1-methyl- pyran-4,4- 3S-ylindazol-5-yl diyl 928 tetrahydro- azetidin-3- C(O)O methyl b = 0benzofuran-5-yl pyran-4,4- yl diyl 930 tetrahydro- azetidin-3- C(O)thiazol-2-yl b = 0 quinolin-7-yl furan-3,3- yl diyl 931 1- pyrrolidin-C(O) methyl b = 0 benzofuran-5-yl methoxycar- 3S-yl bonyl)- azetidin-3,3-diyl 932 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0benzofuran-5-yl furan-3,3- yl diyl 933 tetrahydro- pyrrolidin- SO₂methyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 934tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-ylfuran-3,3- 3-yl diyl 935 tetrahydro- azetidin-3- C(O) trifluoromethyl b= 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 937 tetrahydro-azetidin-3- C(O) trifluoromethyl b = 0 1-methyl- furan-3,3- ylindazol-5-yl diyl 938 tetrahydro- pyrrolidin- C(O) trifluoromethyl b = 0benzofuran-5-yl furan-3,3- 3-yl diyl 941 tetrahydro- azetidin-3- C(O)Omethyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 942 tetrahydro-azetidin-3- SO₂ methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 944tetrahydro- azetidin-3- SO₂ methyl b = 0 1-methyl- furan-3,3- ylindazol-5-yl diyl 945 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 01-methyl- furan-3,3- yl 1-yl indazol-5-yl diyl 946 1- pyrrolidin- C(O)trifluoromethyl b = 0 benzofuran-5-yl (methoxycar- 3R-yl bonyl)-azetidin- 3,3-diyl 947 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0quinolin-7-yl pyran-4,4- yl diyl 949 tetrahydro- azetidin-3- C(O)thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 951 1-isopropyl-azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl piperidin- yl4,4-diyl 952 1- azetidin-3- C(O) cyclopropyl b = 0 1- (trifluoro- yl(trifluoromethyl- methyl- carbonyl)-indol- carbonyl)- 5-yl piperidin-4,4-diyl 953 tetrahydro- pyrrolidin- C(O)O methyl b = 0 1-methyl-pyran-4,4- 3S-yl indazol-5-yl diyl 954 tetrahydro- pyrrolidin- C(O)Omethyl b = 0 benzofuran-5-yl furan-3,3- 3S-yl diyl 955 tetrahydro-pyrrolidin- C(O)O trifluoromethyl b = 0 1-methyl- furan-3,3- 3R-ylindazol-5-yl diyl 956 1- pyrrolidin- SO₂ methyl b = 0 benzofuran-5-yl(methoxycar- 3S-yl bonyl)- azetidin- 3,3-diyl 957 1- pyrrolidin- C(O)thiazol-2-yl b = 0 benzofuran-5-yl (methoxycar- 3R-yl bonyl)- azetidin-3,3-diyl 958 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0benzofuran-5-yl pyran-4,4- 3R-yl diyl 959 tetrahydro- pyrrolidin- C(O)thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 960tetrahydro- pyrrolidin- SO₂ methyl b = 0 quinolin-7-yl pyran-4,4- 3S-yldiyl 961 tetrahydro- azetidin-3- C(O) trifluoromethyl b = 0benzofuran-5-yl pyran-4,4- yl diyl 962 1- pyrrolidin- C(O) thiazol-2-ylb = 0 quinolin-7-yl (methoxycar- 3R-yl bonyl)- azetidin- 3,3-diyl 963 1-pyrrolidin- C(O) methyl b = 0 quinolin-7-yl (methoxycar- 3S-yl bonyl)-azetidin- 3,3-diyl 964 1- azetidin-3- C(O) cyclopropyl b = 0 1-methyl-(trifluoro- yl indazol-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 965tetrahydro- pyrrolidin- C(O) trifluoromethyl b = 0 quinolin-7-ylpyran-4,4- 3R-yl diyl 966 1-(2- pyrrolidin- C(O) cyclopropyl b = 0indazol-5-yl hydroxy- 3R-yl ethyl)-piperidin- 4,4-diyl 967 1-(2-pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl hydroxy- 3R-ylethyl)-piperidin- 4,4-diyl 968 1- pyrrolidin- C(O) cyclopropyl b = 0benzofuran-5-yl (trifluoro- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl969 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-hydroxy- 3S-ylphenyl 970 1- pyrrolidin- C(O) 1-methyl- (methyl- 3R-yl cyclopropyl b =0 indazol-5-yl sulfonyl)- piperidin- 4,4-diyl

In Table 2 below, the

portion of the compound of formula (I) is incorporated into the compoundof formula (I) (as drawn at the beginning of Table 2) and in theorientation as drawn in the Table.

TABLE 2 Representative Compounds of Formula (I)

ID No.

(R⁴)_(b)

341 pyrrolidin-3R-yl

b = 0 indol-5-yl 342 pyrrolidin-3R-yl

b = 0 benzthiazol-5-yl 390 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 397 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 402 pyrrolidin-3R-yl

b = 0 indol-5-yl 419 pyrrolidin-3R-yl

b = 0 indazol-5-yl 420 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 421 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 422 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 423 pyrrolidin-3R-yl

b = 0 indol-5-yl 424 pyrrolidin-3R-yl

b = 0 indazol-5-yl 425 pyrrolidin-3R-yl

b = 0 benzothien-5-yl 426 pyrrolidin-3R-yl

b = 0 indol-6-yl 427 pyrrolidin-3R-yl

b = 0 indazol-4-yl 428 pyrrolidin-3R-yl

b = 0 indol-6-yl 429 pyrrolidin-3R-yl

b = 0 indazol-4-yl 430 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 437 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 438 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 439 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 458 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 459 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 971 azetidin-3-yl

b = 0 6-cyano-naphth-2-yl

TABLE 3 Representative Compounds of Formula (I)

                      ID No.                   R¹ & R² taken together

                      (L¹)_(a)                       R³                      (R⁴)_(b)        

 21 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-bromo-phenyl yl 23 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 pyridin-3-yl yl  56cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 1-methyl- ylpyrazol-4-yl  59 cyclopropyl azetidin- C(O) cyclopropyl b = 0 1-methyl-3-yl pyrazol-4-yl  60 cyclopropyl azetidin- C(O) cyclopropyl b = 0pyridin-3-yl 3-yl  61 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0pyridin-4-yl yl  62 cyclopropyl piperidin-4- C(O) cyclopropyl b = 01-methyl- yl pyrazol-5-yl  65 cyclopropyl pyrrolidin- C(O) cyclopropyl b= 0 1-methyl- 3R-yl pyrazol-4-yl  70 cyclopentyl pyrrolidin- C(O)cyclopropyl b = 0 3-(pyrazol-3-yl) 3R-yl  91 cyclopentyl pyrrolidin-C(O) cyclopropyl b = 0 tetrazol-5-yl 3R-yl 122 cyclopropyl pyrrolidin-C(O) cyclopropyl b = 0 pyridin-3-yl 3R-yl 235 cyclopropyl pyrrolidin-C(O) cyclopropyl b = 0 pyridin-4-yl 3R-yl 267 cyclopropyl pyrrolidin-C(O) 1-methyl- 2- 1-methyl- 3R-yl cyclopropyl methyl pyrazol-4-yl 316cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 1-methyl- 3R-yl methylpyrazol-4-yl 322 cyclopropyl azetidin- C(O) cyclopropyl 2-fluoro1-methyl- 3-yl pyrazol-4-yl 323 cyclopropyl pyrrolidin- C(O) cyclopropyl2-fluoro 1-methyl- 3R-yl pyrazol-4-yl 325 cyclopropyl azetidin- C(O)cyclopropyl 2- 1-isopropyl- 3-yl methyl pyrazol-4-yl 326 cyclopropylazetidin- C(O) cyclopropyl 2- 1-cyclopropyl- 3-yl methyl pyrazol-4-yl327 cyclopropyl azetidin- C(O) cyclopropyl 2-fluoro 1-isopropyl- 3-ylpyrazol-4-yl 328 cyclopropyl azetidin- C(O) cyclopropyl 2-fluoro1-cyclopropyl- 3-yl pyrazol-4-yl 329 cyclopropyl azetidin- C(O)cyclopropyl 2-fluoro 1-cyclobutyl- 3-yl pyrazol-4-yl 330 cyclopropylazetidin- C(O) cyclopropyl 2- 1-cyclobutyl- 3-yl methyl pyrazol-4-yl 331cyclopropyl azetidin- C(O) cyclopropyl b = 0 1-isopropyl- 3-ylpyrazol-4-yl 333 cyclopropyl azetidin- C(O) cyclopropyl 2- 1-methyl-3-yl methyl pyrazol-4-yl 337 cyclopropyl azetidin- C(O) 1-methyl- 2-1-cyclopropyl- 3-yl cyclopropyl methyl pyrazol-4-yl 338 cyclopropylazetidin- C(O) 1-methyl- 2- 1-cyclobutyl- 3-yl cyclopropyl methylpyrazol-4-yl 358 cyclopropyl azetidin- C(O) 1-methyl- 2-fluoro 1-methyl-3-yl cyclopropyl pyrazol-4-yl 362 cyclopropyl pyrrolidin- C(O) 1-methyl-2-fluoro 1-methyl- 3R-yl cyclopropyl pyrazol-5-yl 364 cyclopropylpyrrolidin- C(O) 1-methyl- 2-fluoro 1-methyl- 3R-yl cyclopropylpyrazol-4-yl 371 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2-fluoro1-methyl- 3R-yl cyclopropyl pyrazol-5-yl 379 cyclopropyl pyrrolidin-C(O) 1-hydroxy- 2-fluoro 1-methyl- 3R-yl cyclopropyl pyrazol-4-yl 382cyclopropyl azetidin- C(O) 1-hydroxy- 2-fluoro 1-methyl- 3-ylcyclopropyl pyrazol-4-yl 407 cyclopropyl pyrrolidin- C(O) cyclopropyl b= 0 1-methyl- 3R-yl pyrazol-5-yl 411 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 1-methyl- 3S-yl pyrazol-4-yl 412 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 3-chlorophenyl 3S-yl 413 cyclopropylpyrrolidin- C(O) cyclopropyl b = 0 4-methylphenyl 3S-yl 514 cyclopropylazetidin- C(O) cyclopropyl b = 0 1-methyl- 3-yl pyrazol-5-yl 516cyclopropyl azetidin- C(O) cyclopropyl b = 0 1-isopropyl- 3-ylpyrazol-4-yl 517 cyclopropyl azetidin- C(O) cyclopropyl b = 0 1-methyl-3-yl pyrazol-4-yl 534 cyclopropyl azetidin- C(O) cyclopropyl b = 01-methyl- 3-yl pyrazol-4-yl 542 cyclopropyl azetidin- C(O) cyclopropyl b= 0 1-methyl- 3-yl pyrazol-3-yl 544 cyclopropyl azetidin- C(O)cyclopropyl b = 0 1-isobutyl- 3-yl pyrazol-4-yl 547 cyclopropylazetidin- C(O) cyclopropyl 2-fluoro 1-methyl- 3-yl pyrazol-3-yl 566cyclopropyl azetidin- C(O) 1-methyl- 2-fluoro 1-methyl- 3-yl cyclopropylpyrazol-5-yl 577 cyclopropyl azetidin- C(O) 1-hydroxy- 2-fluoro1-methyl- 3-yl cyclopropyl pyrazol-5-yl 601 cyclopropyl azetidin- C(O)1-methyl- 2- 1- 3-yl cyclopropyl methyl cyclopropylmethyl- pyrazol-3-yl602 cyclopropyl azetidin- C(O) 1-methyl- 2- 1-(2- 3-yl cyclopropylmethyl methylpropyl)- pyrazol-3-yl 623 cyclopropyl pyrrolidin- C(O)1-methyl- 2- 1-methyl- 3R-yl cyclopropyl methyl pyrazol-5-yl 655tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- pyran-4,4-3R-yl pyrazol-4-yl diyl 656 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b =0 1-methyl- pyran-4,4- 3R-yl ethyl pyrazol-4-yl diyl 657 tetrahydro-pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- pyran-4,4- 3R-ylfuran-2R-yl pyrazol-4-yl diyl 658 tetrahydro- pyrrolidin- C(O) methyl b= 0 1-methyl- pyran-4,4- 3S-yl pyrazol-4-yl diyl 659 tetrahydro-pyrrolidin- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- 3R-yl methylpyrazol-4-yl diyl 660 tetrahydro- pyrrolidin- C(O) pyrrolidin-1- b = 01-methyl- pyran-4,4- 3R-yl yl pyrazol-4-yl diyl 676 tetrahydro-pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- furan-3,3- 3R-ylpyrazol-4-yl diyl 677 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 01-methyl- furan-3,3- 3R-yl ethyl pyrazol-4-yl diyl 678 tetrahydro-pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- furan-3,3- 3R-ylfuran-2R-yl pyrazol-4-yl diyl 679 tetrahydro- pyrrolidin- C(O)pyrrolidin-1- b = 0 1-methyl- furan-3,3- 3S-yl yl pyrazol-4-yl diyl 694tetrahydro- azetidin- C(O) cyclopropyl b = 0 1-methyl- pyran-4,4- 3-ylpyrazol-4-yl diyl 695 tetrahydro- azetidin- C(O) 1-hydroxy- b = 01-methyl- pyran-4,4- 3-yl ethyl pyrazol-4-yl diyl 696 tetrahydro-azetidin- C(O) tetrahydro- b = 0 1-methyl- pyran-4,4- 3-yl furan-2R-ylpyrazol-4-yl diyl 697 tetrahydro- azetidin- C(O) pyrrolidin-1- b = 01-methyl- pyran-4,4- 3-yl yl pyrazol-4-yl diyl 710 tetrahydro- azetidin-C(O) cyclopropyl b = 0 1-methyl- furan-3,3- 3-yl pyrazol-4-yl diyl 711tetrahydro- azetidin- C(O) 1-hydroxy- b = 0 1-methyl- furan-3,3- 3-ylethyl pyrazol-4-yl diyl 712 tetrahydro- azetidin- C(O) tetrahydro- b = 01-methyl- furan-3,3- 3-yl furan-2R-yl pyrazol-4-yl diyl 713 tetrahydro-azetidin- C(O) pyrrolidin-1- b = 0 1-methyl- furan-3,3- 3-yl ylpyrazol-4-yl diyl 725 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 01-methyl- carbonyl)- 3R-yl pyrazol-4-yl azetidin- 3,3-diyl 7261-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- carbonyl)- 3R-ylethyl pyrazol-4-yl azetidin- 3,3-diyl 727 1-(methoxy- pyrrolidin- C(O)tetrahydro- b = 0 1-methyl- carbonyl)- 3R-yl furan-2R-yl pyrazol-4-ylazetidin- 3,3-diyl 759 piperidin- azetidin- C(O) cyclopropyl b = 01-methyl- 4,4-diyl 3-yl pyrazol-4-yl 767 1- azetidin- C(O) cyclopropyl b= 0 1-methyl- (isopropyl- 3-yl pyrazol-4-yl carbonyl)- piperidin-4,4-diyl 768 1-(dimethyl- azetidin- C(O) cyclopropyl b = 0 1-methyl-amino- 3-yl pyrazol-4-yl methyl- carbonyl)- piperidin- 4,4-diyl 7691-(methyl- azetidin- C(O) cyclopropyl b = 0 1-methyl- sulfonyl)- 3-ylpyrazol-4-yl piperidin- 4,4-diyl 770 1- azetidin- C(O) cyclopropyl b = 01-methyl- (cyclopropyl- 3-yl pyrazol-4-yl carbonyl)- piperidin- 4,4-diyl771 1- azetidin- C(O) cyclopropyl b = 0 1-methyl- (isopropyl)- 3-ylpyrazol-4-yl piperidin- 4,4-diyl 772 1-(2- azetidin- C(O) cyclopropyl b= 0 1-methyl- hydroxy- 3-yl pyrazol-4-yl ethyl)- piperidin- 4,4-diyl 785cyclopropyl azetidin- C(O) 1-methyl- 2- 1-isobutyl- 3-yl cyclopropylmethyl pyrazol-5-yl 786 cyclopropyl azetidin- C(O) 1-methyl- 2- 1- 3-ylcyclopropyl methyl cyclopropylmethyl- pyrazol-5-yl 812 cyclopropylpiperidin- C(O) cyclopropyl b = 0 4-methyl-phenyl 3S-yl 813 cyclopropylpiperidin- C(O) cyclopropyl b = 0 3-chlorophenyl 3S-yl 815 cyclopropylpiperidin- C(O) cyclopropyl b = 0 1-methyl- 3S-yl pyrazol-4-yl 820cyclopropyl piperidin- C(O) cyclopropyl b = 0 3-chloro-phenyl 3R-yl 821cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-methyl-phenyl 3R-yl 823cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3R-ylpyrazol-4-yl 882 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 5-methyl-3R-yl methyl oxadiazol-2-yl 891 1-methoxy- pyrrolidin- SO₂ methyl b = 01-methyl- carbonyl)- 3S-yl pyrazol-4-yl azetidin- 3,3-diyl 893tetrahydro- azetidin- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- 3-ylmethyl pyrazol-4-yl diyl 894 tetrahydro- pyrrolidin- C(O)O methyl b = 01-methyl- furan-3,3- 3S-yl pyrazol-4-yl diyl 899 tetrahydro- azetidin-C(O) trifluoro- b = 0 1-methyl- furan-3,3- 3-yl methyl pyrazol-4-yl diyl901 tetrahydro- azetidin- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3-3-yl pyrazol-4-yl diyl 906 1-methoxy- pyrrolidin- C(O)O methyl b = 01-methyl- carbonyl)- 3S-yl pyrazol-4-yl azetidin- 3,3-diyl 911tetrahydro- azetidin- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3-ylpyrazol-4-yl diyl 918 tetrahydro- pyrrolidin- SO₂ methyl b = 0 1-methyl-pyran-4,4- 3S-yl pyrazol-4-yl diyl 919 1-methoxy- pyrrolidin- C(O)trifluoro- b = 0 1-methyl- carbonyl)- 3R-yl methyl pyrazol-4-ylazetidin- 3,3-diyl 921 tetrahydro- azetidin- SO₂ methyl b = 0 1-methyl-pyran-4,4- 3-yl pyrazol-4-yl diyl 924 1-methoxy- pyrrolidin- C(O)pyrrolidin-1- b = 0 1-methyl- carbonyl)- 3S-yl yl pyrazol-4-yl azetidin-3,3-diyl 927 tetrahydro- azetidin- C(O)O methyl b = 0 1-methyl-furan-3,3- 3-yl pyrazol-4-yl diyl 929 1-methoxy- pyrrolidin- C(O)thiazol-2-yl b = 0 1-methyl- carbonyl)- 3R-yl pyrazol-4-yl azetidin-3,3-diyl 936 tetrahydro- azetidin- C(O)O methyl b = 0 1-methyl-pyran-4,4- 3-yl pyrazol-4-yl diyl 939 tetrahydro- pyrrolidin- SO₂ methylb = 0 1-methyl- furan-3,3- 3-yl pyrazol-4-yl diyl 940 tetrahydro-pyrrolidin- C(O) trifluoro- b = 0 1-methyl- furan-3,3- 3-yl methylpyrazol-4-yl diyl 943 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 01-methyl- furan-3,3- 3-yl pyrazol-4-yl diyl 948 tetrahydro- pyrrolidin-C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3R-yl pyrazol-4-yl diyl 950tetrahydro- azetidin- SO₂ methyl b = 0 1-methyl- furan-3,3- 3-ylpyrazol-4-yl diyl

TABLE 4 Representative Compounds of Formula (I)

                      ID No.                     R¹ & R² taken together

                      (R⁴)_(b)      

 44 cyclopentyl pyrrolidin-3R-yl b = 0 6-(4-methyl-piperazin-1-yl)-piperidin-3-yl 482 cyclopropyl azetidin-3-yl b = 06-(pyrrolidin-1-yl)- pyridin-3-yl) 509 cyclopropyl azetidin-3-yl b = 06-(imidazol-1-yl)- pyridin-3-yl) 526 cyclopropyl azetidin-3-yl 2-fluoro6-(imidazol-1-yl)- pyridin-3-yl) 806 cyclopropyl azetidin-3-yl b = 06-(morpholin-4-yl)- pyridin-3-yl) 828 cyclopentyl pyrrolidin-3R-yl b = 02-(piperazin-1-yl)- pyridin-4-yl) 829 cyclopentyl pyrrolidin-3R-yl b = 02-(4-methylpiperazin-1- yl)-piperidin-4-yl 838 cyclopropyl azetidin-3-ylb = 0 1-(oxetan-3-yl)-pyrazol- 4-yl

In an embodiment, the present invention is directed to compounds offormula (I) as herein described provided that the compound of formula(I) is other than one or more of compounds independently selected fromthe group as listed in Table 5, below.

TABLE 5

                      ID No.                   R¹ & R² taken together

                      (L¹)_(a)                       R³                      (R⁴)_(b)                       R⁵  8 cyclopropyl piperidin-4- C(O)cyclopropyl b = 0 4-(1-methyl- yl pyrazol-5-yl)  9 cyclopropylpiperidin-4- C(O) cyclopropyl b = 0 4-(1-methyl- yl pyrazol-4-yl)  13cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-(1-methyl- 3R-ylpyrazol-4-yl)  32 cyclopropyl piperidin-4- C(O) cyclopropyl b = 04-(pyridin-4-yl) yl  37 cyclopropyl piperidin-4- C(O) cyclopropyl b = 04-(benzoxazol-5- yl yl)  42 cyclopropyl azetidin-3- C(O) cyclopropyl b =0 4-(1-methyl- yl pyrazol-4-yl)  44 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 6-(4-methyl- 3R-yl piperazin-1-yl)- pyridin-3-yl  62cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(1-methyl- ylpyrazol-5-yl)- phenyl  91 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 04-(tetrazol-5-yl)- 3R-yl phenyl 107 cyclopropyl piperidin-4- C(O)cyclopropyl b = 0 4-(4-trifluoro- yl methyl-phenyl) 160 1-(methyl-pyrrolidin- C(O) cyclopropyl b = 0 4-(1,2,3,4- carbonyl)- 3R-yltrihydro-2- piperidin- methyl-carbonyl- 4,4-diyl isoquinolin-6-yl) 1611-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 4-(1,2,3,4- carbonyl)-3R-yl 4a,8a- piperidin- hexahydro-2- 4,4-diyl methyl-carbonyl-isoquinolin-6-yl) 189 cyclopentyl pyrrolidin- SO₂ pyrrolidin-1- b = 04-(benzofuran-5- 3S-yl yl yl) 776 cyclopropyl azetidin-3- C(O)cyclopropyl 2- 3- yl methyl isopropylsulfonyl- phenyl 784 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 6-isopropyl- yl pyridin-3-yl 785cyclopropyl azetidin-3- C(O) 1-methyl- 2- 4-(1-isobutyl- yl cyclopropylmethyl pyrazol-5-yl)- phenyl 788 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 1-oxetan-3-yl- yl indazol-5-yl 789 cyclopropylazetidin-3- C(O) cyclopropyl 2- 1-oxetan-3-yl- yl fluoro indazol-5-yl791 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-methyl-7- ylbeomo-quinolin- 2-yl 793 cyclopropyl azetidin-3- C(O) cyclopropyl b = 03-methyl- yl [1,2,4]triazolo[4, 3-a]pyridin-6-yl 794 cyclopropylazetidin-3- C(O) cyclopropyl b = 0 5-(2-hydroxy-2- yl methyl-propyl)-pyrid-2-yl 796 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- ylcyclopropyl methyl indazol-5-yl 797 cyclopropyl azetidin-3- C(O)cyclopropyl b = 0 6-(2-hydroxy-2- yl methyl-propyl)- pyridin-3-yl 800cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(1-cyano- ylcyclopropyl)- pyrid-3-yl 801 cyclopropyl azetidin-3- C(O) cyclopropyl b= 0 1,5-naphthyridin- yl 3=yl 802 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 5-chloro-pyridin- 3R-yl 3-yl 805 cyclopropylazetidin-3- C(O) pyridin-3-yl 2- 1-methyl- yl methyl indazol-5-yl 806cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(morpholin-4- ylyl)pyridin-3-yl 807 cyclopropyl azetidin-3- C(O) cyclopropyl b = 01-isopropyl- yl indazol-5-yl 809 cyclopropyl pyrrolidin- C(O)cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro-quinolin- 7-yl 812cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-(4-methyl- 3S-ylphenyl)-phenyl 813 cyclopropyl piperidin- C(O) cyclopropyl b = 04-(3-chloro- 3S-yl phenyl)-phenyl 815 cyclopropyl piperidin- C(O)cyclopropyl b = 0 4-(1-methyl- 3S-yl pyrazol-4-yl)- phenyl 816cyclopropyl piperidin- C(O) cyclopropyl b = 0 indazol-5-yl 3S-yl 817cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3S-yl 818cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl 819cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3S-ylindazol-5-yl 821 cyclopropyl piperidin- C(O) cyclopropyl b = 04-(4-methyl- 3R-yl phenyl)-phenyl 822 cyclopentyl pyrrolidin- C(O)cyclopropyl 2- 4-methyl-3,4- 3R-yl methyl dihydro-2H- pyrido[3,2-b][1,4]oxazin-7- yl 828 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 02-(piperazin-1- 3R-yl yl)piperidin-4-yl 829 cyclopentyl pyrrolidin- C(O)cyclopropyl b = 0 2-(4- 3R-yl methylpiperazin- 1-yl)-pyridin-4-yl 859cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-trifluoromethyl- ylphenyl 888 tetrahydro- azetidin-3- SO2 methyl b = 0 benzofuran-5-ylpyran-4,4- yl diyl 891 1-methoxy- pyrrolidin- SO2 methyl b = 04-(1-methyl- carbonyl)- 3S-yl pyrazol-4-yl)- azetidin-3,3- phenyl diyl892 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3-3R-yl indazol-5-yl diyl 893 tetrahydro- azetidin-3- C(O) trifluoro- b =0 4-(1-methyl- pyran-4,4- yl methyl pyrazol-4-yl)- diyl phenyl 894tetrahydro- pyrrolidin- C(O)O methyl b = 0 4-(1-methyl- furan-3,3- 3S-ylpyrazol-4-yl)- diyl phenyl 895 tetrahydro- azetidin-3- C(O) trifluoro- b= 0 quinolin-7-yl furan-3,3- yl methyl diyl 896 tetrahydro- pyrrolidin-SO2 methyl b = 0 quinolin-7-yl furan-3,3- 3-yl diyl 897 tetrahydro-azetidin-3- C(O) trifluoro- b = 0 benzofuran-5-yl furan-3,3- yl methyldiyl 898 tetrahydro- azetidin-3- SO2 methyl b = 0 benzofuran-5-ylfuran-3,3- yl diyl 899 tetrahydro- azetidin-3- C(O) trifluoro- b = 04-(1-methyl- furan-3,3- yl methyl pyrazol-4-yl)- diyl phenyl 900 1-pyrrolidin- SO2 methyl b = 0 quinolin-7-yl methoxycarbonyl)- 3S-ylazetidin-3,3- diyl 901 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 04-(1-methyl- furan-3,3- yl pyrazol-4-yl)- diyl phenyl 902 tetrahydro-azetidin-3- SO2 methyl b = 0 1-methyl- pyran-3,3- yl indazol-5-yl diyl903 tetrahydro- azetidin-3- C(O)O methyl b = 0 quinolin-7-yl furan-3,3-yl diyl 904 tetrahydro- azetidin-3- C(O)O methyl b = 0 benzofuran-5-ylfuran-3,3- yl diyl 905 tetrahydro- azetidin-3- C(O)O methyl b = 01-methyl- furan-3,3- yl indazol-5-yl diyl 906 1-methoxy- pyrrolidin-C(O)O methyl b = 0 4-(1-methyl- carbonyl)- 3S-yl pyrazol-4-yl)-azetidin-3,3- phenyl diyl 907 1-methoxy- pyrrolidin- C(O) trifluoro- b =0 1-methyl- carbonyl)- 3R-yl methyl indazol-5-yl azetidin-3,3- diyl 908tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- ylindazol-5-yl diyl 909 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 01-methyl- furan-3,3- yl indazol-5-yl diyl 910 tetrahydro- azetidin-3-C(O) trifluoro- b = 0 quinolin-7-yl pyran-4,4- yl methyl diyl 911tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 4-(1-methyl- pyran-4,4-yl pyrazol-4-yl)- diyl phenyl 912 tetrahydro- azetidin-3- SO2 methyl b =0 quinolin-7-yl pyran-4,4- yl diyl 913 tetrahydro- pyrrolidin- SO2methyl b = 0 benzofuran-5-yl pyran-4,4- 3S-yl diyl 914 tetrahydro-pyrrolidin- SO2 methyl b = 0 benzofuran-5-yl furan-3,3- 3S-yl diyl 915tetrahydro- pyrrolidin- C(O)O methyl b = 0 1-methyl- furan-3,3- 3S-ylindazol-5-yl diyl 916 1-methoxy- pyrrolidin- C(O)O methyl b = 01-methyl- carbonyl)- 3S-yl indazol-5-yl azetidin-3,3- diyl 9171-methoxy- pyrrolidin- SO2 methyl b = 0 1-methyl- carbonyl)- 3S-ylindazol-5-yl azetidin-3,3- diyl 918 tetrahydro- pyrrolidin- SO2 methyl b= 0 4-(1-methyl- pyran-4,4- 3S-yl pyrazol-4-yl)- diyl phenyl 9191-methoxy- pyrrolidin- C(O) trifluoro- b = 0 4-(1-methyl- carbonyl)-3R-yl methyl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 921 tetrahydro-azetidin-3- SO2 methyl b = 0 4-(1-methyl- pyran-4,4- yl pyrazol-4-yl)-diyl phenyl 923 1-methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl-carbonyl)- 3R-yl indazol-5-yl azetidin-3,3- diyl 925 cyclopropylpiperidin- C(O) cyclopropyl b = 0 4-hydroxy- 3R-yl phenyl 926tetrahydro- pyrrolidin- SO2 methyl b = 0 1-methyl- pyran-4,4- 3S-ylindazol-5-yl diyl 927 tetrahydro- azetidin-3- C(O)O methyl b = 04-(1-methyl- furan-3,3- yl pyrazol-4-yl)- diyl phenyl 928 tetrahydro-azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 9291-methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl- carbonyl)-3R-yl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 930 tetrahydro-azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl furan-3,3- yl diyl 932tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 benzofuran-5-ylfuran-3,3- yl diyl 933 tetrahydro- pyrrolidin- SO2 methyl b = 01-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 934 tetrahydro- pyrrolidin-C(O) thiazol-2-yl b = 0 benzofuran-5-yl furan-3,3- 3-yl diyl 935tetrahydro- azetidin-3- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- ylmethyl indazol-5-yl diyl 936 tetrahydro- azetidin-3- C(O)O methyl b = 04-(1-methyl- pyran-4,4- yl pyrazol-4-yl)- diyl phenyl 937 tetrahydro-azetidin-3- C(O) trifluoro- b = 0 1-methyl- furan-3,3- yl methylindazol-5-yl diyl 939 tetrahydro- pyrrolidin- SO2 methyl b = 04-(1-methyl- furan-3,3- 3-yl pyrazol-4-yl)- diyl phenyl 941 tetrahydro-azetidin-3- C(O)O methyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl942 tetrahydro- azetidin-3- SO2 methyl b = 0 quinolin-7-yl furan-3,3- yldiyl 943 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl-furan-3,3- 3-yl pyrazol-4-yl)- diyl phenyl 944 tetrahydro- azetidin-3-SO2 methyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 947tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl pyran-4,4-yl diyl 948 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl-pyran-4,4- 3R-yl pyrazol-4-yl)- diyl phenyl 949 tetrahydro- azetidin-3-C(O) thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 950tetrahydro- azetidin-3- SO2 methyl b = 0 4-(1-methyl- furan-3,3- ylpyrazol-4-yl)- diyl phenyl 954 tetrahydro- pyrrolidin- C(O)O methyl b =0 benzofuran-5-yl furan-3,3- 3S-yl diyl 956 1-(methoxy- pyrrolidin- SO2methyl b = 0 benzofuran-5-yl carbonyl)- 3S-yl azetidin-3,3- diyl 9571-(methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-ylcarbonyl)- 3R-yl azetidin-3,3- diyl 958 tetrahydro- pyrrolidin- C(O)thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 959 tetrahydro-pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3R-ylindazol-5-yl diyl 960 tetrahydro- pyrrolidin- SO2 methyl b = 0quinolin-7-yl pyran-4,4- 3S-yl diyl 961 tetrahydro- azetidin-3- C(O)trifluoro- b = 0 benzofuran-5-yl pyran-4,4- yl methyl diyl

The present invention is further directed to intermediates in thesynthesis of the compounds of formula (I), as described in more detailherein. In a preferred embodiment, the present invention is directed tocompounds of formula (XVIII)

wherein R¹, R², R⁴, b,

and LG² are as herein defined. In another preferred embodiment, thepresent invention is directed to compounds of formula (XXI)

wherein R¹, R², R⁴, b, m, n,

and LG² are as herein defined. In another preferred embodiment, thepresent invention is directed to compounds of formula (XXIII)

wherein R¹, R², R³, R⁴, L¹, b, m, n,

and LG² are as herein defined. In another preferred embodiment, thepresent invention is directed to compounds of formula (XXV)

wherein R¹, R², R⁴, R⁵, b and

are as herein defined. In another preferred embodiment, the presentinvention is directed to compounds of formula (XXVII)

wherein R¹, R², R⁴, R⁵, b, m, n,

are as herein defined.

Definitions

As used herein, unless otherwise noted, the term “halogen” means chloro,bromo, fluoro, and iodo. Preferably, the halogen is bromo, chloro orfluoro.

As used herein, unless otherwise noted, the term “oxo” when used todefine a substituent group means an oxygen atom which is bound to achain or ring carbon atom through a double bond (i.e. ═O).

As used herein, the term “C_(X-Y)alkyl” whether used alone or as part ofa substituent group, means any straight and branched carbon chaincomposition of between X and Y carbon atoms. For example, “C₁₋₆alkyl”means any straight or branched carbon chain composition of between 1 and6 carbon atoms, including, but not limited to, methyl, ethyl, propyl,isopropyl, butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, andthe like.

One skilled in the art will recognize that the term “—(C_(X-Y)alkyl)-”denotes any C_(X-Y)alkyl carbon chain as herein defined, wherein saidC_(X-Y)alkyl chain is divalent and is bound through two points ofattachment, preferably through two terminal carbon atoms. For example,“—(C₁₋₄alkyl)-” includes, but is not limited to —CH₂—, —CH₂CH₂—,—CH(CH₃)—, —CH₂CH₂CH₂—, —CH₂CH(CH₃)—, —CH₂CH₂CH₂CH₂—, CH₂CH(CH₃)CH₂—,and the like.

As used herein, unless otherwise noted, the term “halogenatedC_(X-Y)alkyl” means any C_(X-Y)alkyl group as defined above substitutedwith at least one halogen atom, preferably at least one fluoro atom. Forexample, “halogenated C₁₋₄alkyl” includes, but is not limited to, —CF₃,—CCl₃, —CH₂I, —CH₂Br, —CH₂—CF₃, —CH₂—CCl₃, —CF₂—CF₂—CF₂—CF₃, and thelike. Similarly, as used herein, unless otherwise noted, the term“fluorinated C_(X-Y)alkyl” means any C_(X-Y)alkyl group as defined abovesubstituted with at least one fluoro atom. For example, the term“fluorinated C₁₋₄alkyl” includes, but is not limited to —CF₃, —CH₂—CF₃,—CF₂—CF₂—CF₂—CF₃, and the like.

As used herein, unless otherwise noted, the term “hydroxy substitutedC_(X-Y)alkyl” means C_(X-Y)alkyl group as defined above substituted withat least one hydroxy group. Preferably, the C_(X-Y)alkyl group issubstituted with one hydroxy group. Preferably, the C_(X-Y)alkyl groupis substituted with a hydroxy group at the terminal carbon. For example,the term “hydroxy substituted C₁₋₄alkyl” includes, but is not limitedto, —CH₂(OH), —CH₂—CH₂(OH), —CH₂—CH(OH)—CH₂, and the like.

As used herein, the term “C_(X-Y)alkenyl” whether used alone or as partof a substituent group, means any straight and branched carbon chaincomposition of between X and Y carbon atoms comprising at least oneunsaturated double bond. For example, “C₂₋₄alkyl” means any straight orbranched carbon chain composition of between 2 and 4 carbon atoms,comprising at least one double bond. Suitably examples include, but arenot limited to, —CH═CH₂, —CH₂—CH═CH₂, —CH═CH₂—CH₃, —CH₂—CH₂—CH═CH₂,—CH₂—CH═CH—CH₃, and the like.

As used herein, unless otherwise noted, “C_(X-Y)alkoxy” wherein X and Yare integers, denotes an oxygen ether radical of the above describedstraight or branched chain C_(X-Y)alkyl groups. For example, the term“C₁₋₄alkoxy” includes, but is not limited to methoxy, ethoxy, n-propoxy,sec-butoxy, t-butoxy, n-hexyloxy and the like.

As used herein, unless otherwise noted, the term “halogenatedC_(X-Y)alkoxy” wherein X and Y are integers means any oxygen etherradical as defined above substituted with at least one halogen atom,preferably at least one fluoro atom. For example, the term “halogenatedC₁₋₄alkoxy” includes, but is not limited to, —OCF₃, —OCCl₃, —OCH₂I,—OCH₂Br, —OCH₂—CF₃, —OCH₂—CCl₃, OF₂—CF₂—CF₂—CF₃, and the like.Similarly, as used herein, unless otherwise noted, the term “fluorinatedC_(X-Y)alkoxy” means any oxygen ether radical as defined abovesubstituted with at least one fluoro atom. For example, the term“fluorinated C₁₋₄alkoxy” includes, but is not limited to —OCF₃,—OCH₂—CF₃, —OCF₂—CF₂—CF₂—CF₃, and the like.

As used herein, unless otherwise noted, the term “C_(X-Y)cycloalkyl”wherein X and Y are integers means any stable saturated ring systemcomprising between X and Y carbon ring atoms. For example, the term“C₁₋₈cycloalkyl” means any stable 3 to 8-membered saturated ringstructure, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,cycloheptyl and cyclooctyl.

As used herein, unless otherwise noted, the term “benzo-fusedC_(X-Y)cycloalkyl” wherein X and Y are integers, means any stablemonocyclic, saturated ring structure comprising between X and Y carbonring atoms, which saturated ring structure is benzo-fused. Suitableexamples include 2,3-dihydro-1H-indenyl and 1,2,3,4-tetrahydro-naphthyl.

As used herein, unless otherwise noted, “aryl” means any carbocylicaromatic ring structure as phenyl, naphthyl, and the like. Preferably,the aryl is phenyl or naphthyl, more preferably phenyl.

As used herein, unless otherwise noted, “heteroaryl” denotes any five orsix-membered monocyclic aromatic ring structure containing at least oneheteroatom selected from the group consisting of O, N and S, optionallycontaining one to three additional heteroatoms independently selectedfrom the group consisting of O, N and S; or any nine or ten-memberedbicyclic aromatic ring structure containing at least one heteroatomselected from the group consisting of O, N and S, optionally containingone to four additional heteroatoms independently selected from the groupconsisting of O, N and S; and wherein the heteroaryl contains one ofmore S heteroatom(s), said S heteroatom(s) are each independentlyoptionally substituted with one to two oxo groups. The heteroaryl groupmay be attached at any heteroatom or carbon atom of the ring such thatthe result is a stable structure.

Examples of suitable heteroaryl groups include, but are not limited to,pyrrolyl, furyl, thienyl, oxazolyl, imidazolyl, purazolyl, isoxazolyl,isothiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridinyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furazanyl, indolizinyl,indolyl, isoindolinyl, indazolyl, benzofuranyl, benzothienyl,benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolizinyl,quinolinyl, isoquinolinyl, isothiazolyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl,pyrrolo[2,3-b]pyridinyl, pyrazolo[4,3-b]pyridinyl,[1,2,4]triazo[4,3-a]pyridinyl, and the like.

As used herein, unless otherwise noted, the term “5 to 6-memberedheteroaryl” denotes any five or six membered monocyclic aromatic ringstructure containing at least one heteroatom selected from the groupconsisting of O, N and S, optionally containing one to three additionalheteroatoms independently selected from the group consisting of O, N andS; wherein the 5 to 6-membered heteroaryl contains one of more Sheteroatom(s), said S heteroatom(s) are each independently optionallysubstituted with one to two oxo groups. The 5 to 6-membered heteroarylmay be attached at any heteroatom or carbon atom of the ring such thatthe result is a stable structure. Suitable examples include, but are notlimited to, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, imidazolyl,purazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl,tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl,furazanyl, and the like. Preferred 5 to 6-membered heteroaryl includeone or more selected from the group consisting of pyrrolyl, furanyl,thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazoly, triazolyl,tetrazolyl, pyridinyl, pyrimidinyl, pyrazonyl, and pyranyl.

As used herein, unless otherwise noted, the term “6-membered, nitrogencontaining heteroaryl” denotes any six-membered monocyclic aromatic ringstructure containing at least one N heteroatom, optionally containingone to three additional heteroatoms independently selected from thegroup consisting of O and N. The 6-membered heteroaryl may be attachedat any heteroatom or carbon atom of the ring such that the result is astable structure. Suitable examples include, but are not limited to,pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furazanyl, andthe like.

As used herein, unless otherwise noted, the term “9 to 10-memberedheteroaryl” denotes any nine or ten-membered bicyclic aromatic ringstructure containing at least one heteroatom selected from the groupconsisting of O, N and S, optionally containing one to four additionalheteroatoms independently selected from the group consisting of O, N andS; wherein the 9 to 10-membered heteroaryl contains one of more Sheteroatom(s), said S heteroatom(s) are each independently optionallysubstituted with one to two oxo groups. The 9 to 10-membered heteroarylmay be attached at any heteroatom or carbon atom of the ring such thatthe result is a stable structure. Suitable examples include, but are notlimited to, indolizinyl, indolyl, isoindolinyl, indazolyl, benzofuranyl,benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl,quinolizinyl, quinolinyl, isoquinolinyl, isothiazolyl, cinnolinyl,phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl,pyrrolo[2,3-b]pyridinyl, pyrazolo[4,3-b]pyridinyl,[1,2,4]triazo[4,3-a]pyridinyl, and the like.

As used herein, the term “heterocycyl” denotes any four toeight-membered monocyclic, saturated or partially unsaturated ringstructure containing at least one heteroatom selected from the groupconsisting of O, N and S, optionally containing one to three additionalheteroatoms independently selected from the group consisting of O, N andS; or a nine to ten-membered saturated, partially unsaturated orpartially aromatic (e.g. benzo-fused) bicyclic ring system containing atleast one heteroatom selected from the group consisting of 0, N and S,optionally containing one to four additional heteroatoms independentlyselected from the group consisting of O, N and S; and wherein theheterocyclcyl contains one of more S heteroatom(s), said S heteroatom(s)are each independently optionally substituted with one to two oxogroups. The heterocyclyl group may be attached at any heteroatom orcarbon atom of the ring such that the result is a stable structure.

Suitably examples include, but are not limited to, pyrrolinyl,pyrrolidinyl, dioxalanyl, imidazolinyl, imidazolidinyl, pyrazolinyl,pyrazolidinyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl,thiomorpholinyl, piperazinyl, trithianyl, azepanyl, 1,4-diazepanyl,1,4-oxazepanyl, indolinyl, isoindolinyl, chromenyl,3,4-methylenedioxyphenyl, 2,3-dihydrobenzofuranyl, tetrahydro-furanyl,and the like. Preferred heterocycloalkyl groups include one or moreselected from the group consisting of pyrrolidinyl, dioxalkanyl,imidazolidinyl, pyrazolinyl, pyrazolidinyl, piperidinyl, morpholinyl,piperazinyl, azepanyl, 1,4-diazepanyl, 1,4-oxazepanyl, indolinyl,2,3-dihydro-furanyl and tetrahydro-furanyl.

As used herein, unless otherwise noted, the term “5 to 6-memberedsaturated heterocyclyl” denotes any 5 to 6-membered monocyclic,saturated ring structure containing at least one heteroatom selectedfrom the group consisting of O, S and N, optionally containing one tothree additional heteroatoms independently selected from the groupconsisting of O, S and N; and wherein the 5 to 6-membered saturatedheterocyclyl contains one or more S heteroatom(s), said S heteroatom(s)are each independently, optionally substituted with one to two oxogroups. The 5 to 6-membered saturated heterocyclyl group may be attachedat any heteroatom or carbon atom of the ring such that the result is astable structure. Suitable examples include, but are not limited toSuitably examples include, but are not limited to, pyrrolidinyl,dioxolanyl, imidazolidinyl, pyrazolidinyl, piperidinyl, 1,4-dioxanyl,morpholinyl, 1,4-dithianyl, thiomorpholinyl, piperazinyl, azepanyl,1,4-diazepanyl, 1,4-oxazapanyl, and the like. Preferably, the 5 to6-membered saturated heterocyclyl include one or more selected from thegroup consisting of pyrrolidinyl, dioxolanyl, piperidinyl, 1,4-dioxanyl,morpholinyl, piperazinyl, azepanyl, 1,4-diazepanyl and 1,4-oxazapanyl.

As used herein, unless otherwise noted, the term “partially unsaturatedheteroaryl” denotes any five to seven-membered monocyclic partiallyunsaturated ring structure containing at least one unsaturated (e.g.double) bond and further containing at least one heteroatom selectedfrom the group consisting of O, N and S, optionally containing one tothree additional heteroatoms independently selected from the groupconsisting of O, N and S; or a nine to eleven-membered partiallyunsaturated or partially aromatic (e.g. benzo-fused) bicyclic ringsystem containing at least one unsaturated (e.g. double) bond andfurther containing at least one heteroatom selected from the groupconsisting of O, N and S, optionally containing one to four additionalheteroatoms independently selected from the group consisting of O, N andS; and wherein the partially unsaturated heterocyclyl contains one ofmore S heteroatom(s), said S heteroatom(s) are each independentlyoptionally substituted with one to two oxo groups. The partiallyunsaturated heterocyclyl may be attached at any heteroatom or carbonatom of the ring such that the result is a stable structure. Suitablyexamples include, but are not limited to, indolinyl, isoindolinyl,2,3-dihydrobenzofuranyl, 1,3-dihydroisobenzofuranyl,2,3-dihydrobenzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, chromanyl,isochromanyl, 3,4-dihydro-quinolinyl, 1,2,3,4-tetrahydroquinolinyl,1,2,3,4-tetrahydro-isoquinolinyl, 1,2,3,4,4a,8a-hexahydro-isoquinolinyl,1,2-dihydro-indazolyl, 2,3-dihydro-benzo[1,4]dioxin-6-yl,3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl, and the like.

When a particular group is “substituted” (e.g., C_(X-Y)alkyl,C_(X-Y)cycloalkyl, aryl, heteroaryl, heterocyclyl, etc.) that group mayhave one or more substituents, preferably from one to five substituents,more preferably from one to three substituents, most preferably from oneto two substituents, independently selected from the list ofsubstituents.

With reference to substituents, the term “independently” means that whenmore than one of such substituents is possible, such substituents may bethe same or different from each other.

As used herein, the notation “*” denotes the presence of a stereogeniccenter.

Where the compounds according to this invention have at least one chiralcenter, they may accordingly exist as enantiomers. Where the compoundspossess two or more chiral centers, they may additionally exist asdiastereomers. It is to be understood that all such isomers and mixturesthereof are encompassed within the scope of the present invention.Preferably, when the compound is present as an enantiomer, theenantiomer is present at an enantiomeric excess of greater than or equalto about 80%, more preferably, at an enantiomeric excess of greater thanor equal to about 90%, more preferably still, at an enantiomeric excessof greater than or equal to about 95%, more preferably still, at anenantiomeric excess of greater than or equal to about 98%, mostpreferably, at an enantiomeric excess of greater than or equal to about99%. Similarly, when the compound is present as a diastereomer, thediastereomer is present at an diastereomeric excess of greater than orequal to about 80%, more preferably, at an diastereomeric excess ofgreater than or equal to about 90%, more preferably still, at andiastereomeric excess of greater than or equal to about 95%, morepreferably still, at an diastereomeric excess of greater than or equalto about 98%, most preferably, at an diastereomeric excess of greaterthan or equal to about 99%.

Furthermore, some of the crystalline forms for the compounds of thepresent invention may exist as polymorphs and as such are intended to beincluded in the present invention. In addition, some of the compounds ofthe present invention may form solvates with water (i.e., hydrates) orcommon organic solvents, and such solvates are also intended to beencompassed within the scope of this invention.

Furthermore, it is intended that within the scope of the presentinvention, any element, in particular when mentioned in relation to acompound of formula (I), shall comprise all isotopes and isotopicmixtures of said element, either naturally occurring or syntheticallyproduced, either with natural abundance or in an isotopically enrichedform. For example, a reference to hydrogen includes within its scope ¹H,²H (D), and ³H (T). Similarly, references to carbon and oxygen includewithin their scope respectively ¹²C, ¹³C and ¹⁴C and ¹⁶O and ¹⁸O. Theisotopes may be radioactive or non-radioactive. Radiolabelled compoundsof formula (I) may comprise a radioactive isotope selected from thegroup of ³H, ¹¹C, ¹⁸F, ¹²²I, ¹²³I, ¹²⁵I, ¹³¹I, ⁷⁵Br, ⁷⁷Br and ⁸²Br.Preferably, the radioactive isotope is selected from the group of ³H, ICand ¹⁸F.

Unless otherwise denoted through use of a “-” symbol, under standardnomenclature used throughout this disclosure, the terminal portion ofthe designated side chain is described first, followed by the adjacentfunctionality toward the point of attachment. Thus, for example, a“phenylC₁-C₆alkylaminocarbonylC₁-C₆alkyl” substituent refers to a groupof the formula

Abbreviations used in the specification, particularly the Schemes andExamples, are as follows:

-   AcOH or HOAc=Acetic acid-   Boc or BOC=tert-Butoxycarbonyl-   BSA=Bovine Serum Albumin-   Cbz=Carboxybenzyl-   CDI=Carbonyldiimidazole-   CoA=Acetyl coenzyme-A-   Cu(OAc)₂=Copper Acetate-   DCE=Dichloroethane-   DCM=Dichloromethane-   DIPEA or DIEA=Diisopropylethylamine-   DMAP=4-N,N-Dimethylaminopyridine-   DME=Dimethyl Ether-   DMF=N,N-Dimethylformamide-   DMP or    Dess-Martin=1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-Periodinane    3(1H)-one-   DMSO=Dimethylsulfoxide-   DTT=Dithiothreiito-   EDAC or EDCI=1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide-   EDTA=Ethylenediaminetetraacetic acid-   Et₃N or TEA=Triethylamine-   Et₂O=Diethyl ether-   EtOAc=Ethyl acetate-   FASN=Fatty Acid Synthase-   FBS Fetal Bovine Serum-   HATU=o-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium    hexafluorophosphate-   HBTU=2-(1H-Benzotriazole-1-yl)-1,1,3,3-Tetramethyluronium    hexafluorophosphate-   hFASN=Human fatty Acid Synthase-   HOBT or HOBt=1-Hydroxybenzotriazole-   HPLC=High Performance Liquid Chromatography-   LHMDS=Lithium Bis(trimethylsilyl)amide-   MeCN=Acetonitrile-   MeOH=Methanol-   MEM=Eagle's minimum essential medium-   Mesylate=Methanesulfonate-   Mesyl=Methanesulfonyl-   MOM=Methoxymethyl-   MS-Cl=Mesyl Chloride-   MTBE=Methyl tert-Butyl Ether-   MTT=Methyl Thiazolyl Tetrazolium-   NADPH Nicotinaride adenine dinucleotide phosphate-   NMP=1-Methyl-2-pyrrolidinone-   PBS=Phosphate-buffered Saline-   Pd/C=Palladium on Carbon Catalyst-   Pd₂(OAc)₂=Palladium(II)acetate-   Pd₂(dba)₂=Bis(dibenzylidene acetone)dipalladium(0)-   Pd(dppf)=Palladium diphenyiphosphinoferrocene-   Pd(PPh₃)₄=Tetrakistriphenylphosphine palladium (0)-   PPh₃=Triphenylphosphine-   RT or rt=Room temperature-   t-BOC or Boc=Tert-Butoxycarbonyl-   t-BuOK=Potassium tert-Butoxide-   TEA=Triethylamine-   TFA=Trifluoroacetic Acid-   THF=Tetrahydro-furan-   THP Tetrahydro-pyranyl-   TMOF=Trimethylorthoformate-   TMS=Trimethylsilyl-   TMS-Cl=Trimethylsilyl chloride-   Tosylate=p-Toluenesulfonate-   Tosyl=p-Toluenesulfonyl-   Triflate or OTf=Trifluoromethanesulfonate-   Triflyl=Trifluoromethanesulfonyl

As used herein, unless otherwise noted, the term “isolated form” meansthat the compound is present in a form which is separate from any solidmixture with another compound(s), solvent system, or biologicalenvironment. In an embodiment of the present invention, the compound offormula (I) is present in an isolated form.

As used herein, unless otherwise noted, the term “substantially pureform” means that the mole percent of impurities in the isolated compoundis less than about 5 mole percent, preferably less than about 2 molepercent, more preferably, less than about 0.5 mole percent, mostpreferably, less than about 0.1 mole percent. In an embodiment of thepresent invention, the compound of formula (I) is present as asubstantially pure form.

As used herein, unless otherwise noted, the term “substantially free ofa corresponding salt form(s)” when used to described the compound offormula (I) means that mole percent of the corresponding salt form(s) inthe isolated base of formula (I) is less than about 5 mole percent,preferably less than about 2 mole percent, more preferably, less thanabout 0.5 mole percent, most preferably less than about 0.1 molepercent. In an embodiment of the present invention, the compound offormula (I) is present in a form which is substantially free ofcorresponding salt form(s).

As used herein, unless otherwise noted, the terms “treating”,“treatment” and the like, include the management and care of a subjector patient (preferably mammal, more preferably human) for the purpose ofcombating a disease, condition, or disorder and includes theadministration of a compound of the present invention to prevent theonset of the symptoms or complications, alleviate the symptoms orcomplications, or eliminate the disease, condition, or disorder.

As used herein, unless otherwise noted, the term “prevention” includes(a) reduction in the frequency of one or more symptoms; (b) reduction inthe severity of one or more symptoms; (c) the delay or avoidance of thedevelopment of additional symptoms; (d) delay or avoidance of thedevelopment of the disorder or condition; and/or (f) the delay oravoidance of the progression of the disorder or condition.

One skilled in the art will recognize that when the present invention isdirected to methods of prevention, a subject in need of thereof (i.e. asubject in need of prevention) includes any subject or patient(preferably a mammal, more preferably a human) who has experienced orexhibited at least one symptom of the disorder, disease, or condition tobe prevented. Further, a subject in need thereof may additionally be asubject (preferably a mammal, more preferably a human) who has notexhibited any symptoms of the disorder, disease, or condition to beprevented, but who has been deemed by a physician, clinician, or othermedical profession to be at risk of developing such disorder, disease,or condition. For example, the subject may be deemed at risk ofdeveloping a disorder, disease, or condition (and therefore in need ofprevention or preventive treatment) as a consequence of the subject'smedical history, including, but not limited to, family history,pre-disposition, co-existing (comorbid) disorders or conditions, genetictesting, and the like.

The term “subject” as used herein, refers to an animal, preferably amammal, most preferably a human, who has been the object of treatment,observation or experiment. Preferably, the subject has experiencedand/or exhibited at least one symptom of the disease or disorder to betreated and/or prevented.

The term “therapeutically effective amount” as used herein, means anamount of active compound or pharmaceutical agent that elicits thebiological or medicinal response in a tissue system, animal, or humanthat is being sought by a researcher, veterinarian, medical doctor, orother clinician, which response includes alleviation of the symptoms ofthe disease or disorder being treated.

As used herein, the term “composition” is encompasses a productcomprising, consisting of and/or consisting essentially of the specifiedingredients in the specified amounts, as well as any product thatresults, directly or indirectly, from combinations of the specifiedingredients in the specified amounts.

As more extensively provided in this written description, terms such as“reacting” and “reacted” are used herein in reference to a chemicalentity that is any one of: (a) the actually recited form of suchchemical entity and (b) any of the forms of such chemical entity in themedium in which the compound is being considered when named.

One skilled in the art will recognize that, where not otherwisespecified, the reaction step(s) is performed under suitable conditions,according to known methods, to provide the desired product. One skilledin the art will further recognize that, in the specification and claimsas presented herein, when a reagent or reagent class/type (e.g., base,solvent, etc.) is recited in more than one step of a process, theindividual reagents are independently selected for each reaction stepand may be the same of different from each other. For example when twosteps of a process recite an organic or inorganic base as a reagent, theorganic or inorganic base selected for the first step may be the same ordifferent than the organic or inorganic base of the second step.Further, one skilled in the art will recognize that when a reaction stepof the present invention may be carried out in a variety of solvents orsolvent systems, said reaction step may also be carried out in a mixtureof the suitable solvents or solvent systems.

To provide a more concise description, some of the quantitativeexpressions given herein are not qualified with the term “about”. It isunderstood that whether the term “about” is used explicitly or not,every quantity given herein is meant to refer to the actual given value,and it is also meant to refer to the approximation to such given valuethat would reasonably be inferred based on the ordinary skill in theart, including approximations due to the experimental and/or measurementconditions for such given value.

To provide a more concise description, some of the quantitativeexpressions herein are recited as a range from about amount X to aboutamount Y. It is understood that when a range is recited, the range isnot limited to the recited upper and lower bounds, but rather includesthe full range from about amount X through about amount Y, or any amountor range therein.

Examples of suitable solvents, bases, reaction temperatures, and otherreaction parameters and components are provided in the detaileddescriptions which follow herein. One skilled in the art will recognizethat the listing of said examples is not intended, and should not beconstrued, as limiting in any way the invention set forth in the claimswhich follow thereafter. One skilled in the art will further recognizethat when a reaction step of the present invention may be carried out ina variety of solvents or solvent systems, such reaction step may also becarried out in a mixture of the suitable solvents or solvent systems.

As used herein, unless otherwise noted, the term “aprotic solvent” meansany solvent that does not yield a proton. Suitable examples include, butare not limited to DMF, 1,4-dioxane, THF, acetonitrile, pyridine,dichloroethane, dichloromethane, MTBE, toluene, acetone, and the like.

As used herein, unless otherwise noted, the term “leaving group” means acharged or uncharged atom or group which departs during a substitutionor displacement reaction. Suitable examples include, but are not limitedto, Br, Cl, I, mesylate, tosylate, triflate, and the like.

During any of the processes for preparation of the compounds of thepresent invention, it may be necessary and/or desirable to protectsensitive or reactive groups on any of the molecules concerned. This maybe achieved by means of conventional protecting groups, such as thosedescribed in Protective Groups in Organic Chemistry, ed. J. F. W.McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, ProtectiveGroups in Organic Synthesis, John Wiley & Sons, 1991. The protectinggroups may be removed at a convenient subsequent stage using methodsknown from the art.

As used herein, unless otherwise noted, the term “nitrogen protectinggroup” means a group which may be attached to a nitrogen atom to protectsaid nitrogen atom from participating in a reaction and which may bereadily removed following the reaction. Suitable nitrogen protectinggroups include, but are not limited to carbamates—groups of the formula—C(O)O—R wherein R is for example methyl, ethyl, t-butyl, benzyl,phenylethyl, CH₂═CH—CH₂—, and the like; amides—groups of the formula—C(O)—R′ wherein R′ is for example methyl, phenyl, trifluoromethyl, andthe like; N-sulfonyl derivatives—groups of the formula —SO₂—R″ whereinR″ is for example tolyl, phenyl, trifluoromethyl,2,2,5,7,8-pentamethylchroman-6-yl-, 2,3,6-trimethyl-4-methoxybenzene,and the like. Other suitable nitrogen protecting groups may be found intexts such as T. W. Greene & P. G. M. Wuts, Protective Groups in OrganicSynthesis, John Wiley & Sons, 1991.

As used herein, unless otherwise noted, the term “oxygen protectinggroup” means a group which may be attached to an oxygen atom to protectsuch oxygen atom from participating in a reaction and which may bereadily removed following the reaction. Suitable oxygen protectinggroups include, but are not limited to, acetyl, benzoyl,t-butyl-dimethylsilyl, trimethylsilyl (TMS), methoxymethyl (MOM),tetrahydro-pyranyl (THP), and the like. Other suitable oxygen protectinggroups may be found in texts such as T. W. Greene & P. G. M. Wuts,Protective Groups in Organic Synthesis, John Wiley & Sons, 1991.

Where the processes for the preparation of the compounds according tothe invention give rise to mixture of stereoisomers, these isomers maybe separated by conventional techniques such as preparativechromatography. The compounds may be prepared in racemic form, orindividual enantiomers may be prepared either by enantiospecificsynthesis or by resolution. The compounds may, for example, be resolvedinto their component enantiomers by standard techniques, such as theformation of diastereomeric pairs by salt formation with an opticallyactive acid, such as, (−)-di-p-toluoyl-D-tartaric acid and/or(+)-di-p-toluoyl-L-tartaric acid followed by fractional crystallizationand regeneration of the free base. The compounds may also be resolved byformation of diastereomeric esters or amides, followed bychromatographic separation and removal of the chiral auxiliary.Alternatively, the compounds may be resolved using a chiral HPLC column.

Additionally, chiral HPLC against a standard may be used to determinepercent enantiomeric excess (% ee). The enantiomeric excess may becalculated as follows[(Rmoles−Smoles)/(Rmoles+Smoles)]×100%

where Rmoles and Smoles are the R and S mole fractions in the mixturesuch that Rmoles+Smoles=1. The enantiomeric excess may alternatively becalculated from the specific rotations of the desired enantiomer and theprepared mixture as follows:ee=([α−obs]/[α−max])×100.

The present invention includes within its scope prodrugs of thecompounds of this invention. In general, such prodrugs will befunctional derivatives of the compounds which are readily convertible invivo into the required compound. Thus, in the methods of treatment ofthe present invention, the term “administering” encompasses thetreatment of the various disorders described with the compoundspecifically disclosed or with a compound that may not be specificallydisclosed, but converts to the specified compound in vivo afteradministration to the patient. Conventional procedures for the selectionand preparation of suitable prodrug derivatives are described, forexample, in Design of Prodrugs, ed. H. Bundgaard, Elsevier, 1985.

For use in medicine, the salts of the compounds of this invention referto non-toxic “pharmaceutically acceptable salts.” Other salts may,however, be useful in the preparation of compounds according to thisinvention or of their pharmaceutically acceptable salts. Suitablepharmaceutically acceptable salts of the compounds include acid additionsalts that may, for example, be formed by mixing a solution of thecompound with a solution of a pharmaceutically acceptable acid such ashydrochloric acid, sulfuric acid, fumaric acid, maleic acid, succinicacid, acetic acid, benzoic acid, citric acid, tartaric acid, carbonicacid, or phosphoric acid. Furthermore, where the compounds of theinvention carry an acidic moiety, suitable pharmaceutically acceptablesalts thereof may include alkali metal salts, e.g., sodium or potassiumsalts; alkaline earth metal salts, e.g., calcium or magnesium salts; andsalts formed with suitable organic ligands, e.g., quaternary ammoniumsalts. Thus, representative pharmaceutically acceptable salts include,but are not limited to, the following: acetate, benzenesulfonate,benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calciumedetate, camsylate, carbonate, chloride, clavulanate, citrate,dihydrochloride, edetate, edisylate, estolate, esylate, fumarate,gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate,hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide,isothionate, lactate, lactobionate, laurate, malate, maleate, mandelate,mesylate, methylbromide, methylnitrate, methylsulfate, mucate,napsylate, nitrate, N-methylglucamine ammonium salt, oleate, pamoate(embonate), palmitate, pantothenate, phosphate/diphosphate,polygalacturonate, salicylate, stearate, sulfate, subacetate, succinate,tannate, tartrate, teoclate, tosylate, triethiodide, and valerate.

Representative acids that may be used in the preparation ofpharmaceutically acceptable salts include, but are not limited to, thefollowing: acids including acetic acid, 2,2-dichloroacetic acid,acylated amino acids, adipic acid, alginic acid, ascorbic acid,L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoicacid, (+)-camphoric acid, camphorsulfonic acid,(+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylicacid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid,ethane-1,2-disulfonic acid, ethanesulfonic acid,2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaricacid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucoronicacid, L-glutamic acid, α-oxo-glutaric acid, glycolic acid, hipuric acid,hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lacticacid, lactobionic acid, maleic acid, (−)-L-malic acid, malonic acid,(±)-DL-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid,naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotincacid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid,pamoic acid, phosphoric acid, L-pyroglutamic acid, salicylic acid,4-amino-salicylic acid, sebaic acid, stearic acid, succinic acid,sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid,p-toluenesulfonic acid, and undecylenic acid.

Representative bases which may be used in the preparation ofpharmaceutically acceptable salts include, but are not limited to, thefollowing: bases including ammonia, L-arginine, benethamine, benzathine,calcium hydroxide, choline, deanol, diethanolamine, diethylamine,2-(diethylamino)-ethanol, ethanolamine, ethylenediamine,N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, magnesiumhydroxide, 4-(2-hydroxyethyl)-morpholine, piperazine, potassiumhydroxide, 1-(2-hydroxyethyl)-pyrrolidine, secondary amine, sodiumhydroxide, triethanolamine, tromethamine, and zinc hydroxide.

General Synthetic Schemes

Compounds of formula (I) may be prepared according to the processoutlined in Scheme 1, below.

Accordingly, a suitably substituted compound of formula (X), a knowncompound or compound prepared by known methods, is reacted with NH₃ orwith a suitably substituted compound of formula (XII), wherein PG¹ is asuitably selected nitrogen protecting group such as Boc, Cbz, benzyl,1-phenethyl, and the like; in the presence of a suitably selected sourceof cyanide, such as KCN, NaCN, TMS-CN, and the like; in a suitablyselected solvent or mixture of solvents such as methanol, ethanol,water, and the like; to yield the corresponding compound of formula(XIII), wherein Q¹ is hydrogen or PG¹, respectively.

Alternatively, a suitably substituted compound of formula (XI), whereinA¹ is C₁₋₂alkyl, a known compound or compound prepared by known methods,is reacted with NH₃ or a suitably substituted compound of formula (XII),wherein PG¹ is a suitably selected nitrogen protecting group such asBoc, Cbz, benzyl, 1-phenylethyl, and the like; in the presence of asuitably selected source of cyanide, such as TMS-CN, and the like; in asuitably selected solvent or mixture of solvents such as glacial HOAc,and the like; to yield the corresponding compound of formula (XIII),wherein Q¹ is hydrogen or PG¹, respectively.

The compound of formula (XII) is reacted to yield the correspondingcompound of formula (XV), through a one-step or two step reaction.

Where the compound of formula (XIII) Q¹ is hydrogen, the compound offormula (XIII) is reacted with hydrogen peroxide, in the presence of asuitably selected inorganic base such as K₂CO₃, Na₂CO₃, and the like; ina suitably selected solvent, such as, DMSO, DMF, NMP, and the like; toyield the corresponding compound of formula (XV). Alternatively, thecompound of formula (XII) when Q¹ is hydrogen is reacted with a suitablyselected acid, such as, conc. aq. H₂SO₄, and the like; in a suitablyselected solvent such as DCM, and the like; to yield the correspondingcompound of formula (XV).

Where the compound of formula (XIII) having Q¹ is PG¹, the compound offormula (XII) is reacted with is reacted with hydrogen peroxide in thepresence of a suitably selected inorganic base, such as, K₂CO₃, Na₂CO₃,and the like; in a suitably selected solvent, such as, DMSO, DMF, NMP,and the like; to yield the corresponding compound of formula (XIV),where Q¹ is PG¹. Alternatively, when the compound of formula (XIII)where Q¹ is PG¹ is reacted with a suitably selected acid, such as, conc.aq. H₂SO₄, and the like; in a suitably selected solvent, such as DCM,and the like; to yield the corresponding compound of formula (XIV) whereQ¹ is PG¹. The compound of formula (XIV) is then de-protected accordingto known methods to remove the PG¹ group and yield the correspondingcompound of formula (XV). For example, wherein PG¹ is benzyl, thecompound of formula (XIV) is de-protected by reacting with hydrogen inthe presence of a suitable selected catalyst such as Pd/C, and the like.

The compound of formula (XV) is reacted with a suitably substitutedcompound of formula (XVI), wherein LG¹ is a suitably selected leavinggroup such as Cl, Br, OH, and the like, and wherein LG² is a suitablyselected leaving group such as Cl, Br, OH, triflate, B(OH)₂,B(OC₁₋₂alkyl)₂,

and the like, a known compound or compound prepared by known methods; toyield the corresponding compound of formula (XVII).

More particularly, wherein LG¹ is Cl, Br, and the like, the compound offormula (XV) is reacted with the compound of formula (XVI), in thepresence of a suitably selected organic base such as pyridine, TEA,DIPEA, and the like; optionally in the presence of DMAP, and the like;in a suitably selected solvent such as DCM, DCE, THF, and the like; toyield the corresponding compound of formula (XVII). Alternatively,wherein LG¹ is OH, and the like, the compound of formula (XV) is reactedwith the compound of formula (XVI), in the presence of a suitablyselected coupling reagent such as HATU, HBTU, CDI, EDAC, and the like,in the presence of a suitably selected organic base such as pyridine,TEA, DIPEA, and the like; in a suitably selected organic solvent such asNMP, DMF, DCM, DCE, and the like, to yield the corresponding compound offormula (XVII).

The compound of formula (XVII) is reacted (to effect ring closure) witha suitably selected base such as t-BuOK, NaOH, NaOCH₃, LHMDS, and thelike; in a suitably selected organic solvent or mixture of solvents suchas methanol, ethanol, water, 1,4-dioxane, and the like, and wherein thebase in LHMDS, in a suitably selected organic solvent such as THF, andthe like; to yield the corresponding compound of formula (XVIII).

The compound of formula (XVIII) is reacted with a suitably substitutedcompound of formula (XIX), wherein PG² is a suitably selected nitrogenprotecting group such as Boc, benzyl, Cbz, benzoyl, and the like, andwherein LG³ is a suitably selected leaving group such as Br, I, Cl,mesylate, tosylate, triflate, and the like, a known compound or compoundprepared by known methods; in the presence of a suitably selected basesuch as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solventsuch as DMF, DMP, THF, 1,4-doxane, and the like; to yield thecorresponding compound of formula (XX).

The compound of formula (XX) is then de-protected according to knownmethods to yield the corresponding compound of formula (XXI). Forexample, wherein PG² is Boc, the compound of formula (XXI) isde-protected by reacting with a suitably selected acid, in a suitablyselected organic solvent, for example reacting with HCl in 1,4-dioxane,or reacting with TFA in DCM.

The compound of formula (XXI) is reacted with a suitably substitutedcompound of formula (XXII), a known compound or compound prepared byknown methods, to yield the corresponding compound of formula (XXIII).More particularly, the compound of formula (XXI) is reacted with

(a) a compound of formula (XXII), wherein L^(M) is selected from thegroup consisting of O═C═N(R^(L))— and S═C═N(R^(L))—; in a suitablyselected organic solvent such as DCM, DCE, THF, and the like, to yieldthe corresponding compound of formula (XXIII) wherein L¹ is—C(O)—N(R^(L))— or —C(S)—N(R^(L))—, respectively;

or (b) a compound of formula (XXII), wherein L^(M) is selected from thegroup consisting of Cl—C(O)—N(R^(L))— and Cl—C(S)—N(R^(L))—; in thepresence of a suitably selected organic base such as pyridine, TEA,DIPEA, and the like; optionally in the presence of DMAP, and the like;in a suitably selected solvent such as DCM, DCE, THF, and the like;

or (c) a compound of formula (XXII), wherein L^(M) is selected from thegroup consisting of LG⁴-C(O)—, LG⁴-C(S)—, LG⁴-SO₂— andLG⁴-SO₂—N(R^(L))—, wherein LG⁴ is a suitably selected leaving group suchas Cl, Br, and the like; in the presence of a suitably selected organicbase such as pyridine, TEA, DIPEA, and the like; optionally in thepresence of DMAP, and the like; in a suitably selected solvent such asDCM, DCE, THF, and the like;

or (d) a compound of formula (XXII), wherein L^(M) is selected from thegroup consisting of LG⁴-C(O)—, LG⁴-C(S)—, LG⁴-SO₂— andLG⁴-SO₂—N(R^(L))—, wherein LG⁴ is a suitably selected leaving group suchas OH, and the like, in the presence of a suitably selected couplingreagent such as HATU, HBTU, CDI, EDAC, and the like, in the presence ofa suitably selected organic base such as pyridine, TEA, DIPEA, and thelike; in a suitably selected organic solvent such as NMP, DMF, DCM, DCE,and the like;

to yield the corresponding compound of formula (XXIII).

The compound of formula (XXIII) is reacted with a suitably substitutedcompound of formula (XXIV), wherein the two R groups are each H, areeach the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— toform a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzukicoupling conditions, more particularly, in the presence of a suitablyselected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃,Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presenceof a suitably selected inorganic base such as K₂CO₃, Cs₂CO₃, Na₂CO₃, andthe like; in a suitably selected solvent such as DME, 1,4-dioxane, andthe like, preferably mixed with water; to yield the correspondingcompound of formula (I).

Alternatively, wherein on the compound of formula (XXIII), LG² is OH,the compound of formula (XXIII) may be reacted with triflic anhydride,in the presence of a suitably selected base such as TEA, pyridine, andthe like, in a suitably selected solvent such as DCM, DCE, and the like;to convert the LG² leaving group from OH to triflate; and then reactingthe resulting compound with a suitably substituted compound of formula(XXIV), as described above; to yield the corresponding compound offormula (I).

One skilled in the art will recognize that the R⁵ substituent group mayalternatively be incorporated into the desired compound of formula (I)by reacting a compound of formula (XXIII), wherein the LG² group isreplaced with a group of the formula —B(OR)₂ (wherein the two R groupsare each H, are each the same C₁₋₂alkyl or are taken together as—C(CH₃)₂—C(CH₃)₂— to form a ring (i.e., to form the

with a suitably substituted compound of formula (XXIV), wherein the—B(OR)₂ substitutent is replaced with a suitably selected leaving group,such as Cl, Br, triflate, and the like, under Suzuki couplingconditions, more particularly, in the presence of a suitably selectedcatalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), amixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of asuitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and thelike; in a suitably selected solvent, such as DME, 1,4-dioxane, and thelike, preferably mixed with water.

Compounds of formula (I) may alternatively be prepared according to theprocess as outlined in Scheme 2, below.

Accordingly, a suitably substituted compound of formula (XVII), preparedfor example as outlined in Scheme 1 above, is reacted with a suitablysubstituted compound of formula (XXIV), wherein the two R groups areeach H, are each the same C₁₋₂alkyl or are taken together as—C(CH₃)₂—C(CH₃)₂— to form a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzukicoupling conditions, more particularly, in the presence of a suitablyselected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃,Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presenceof a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃,and the like; in a suitably selected solvent, such as DME, 1,4-dioxane,and the like, preferably mixed with water; to yield the correspondingcompound of formula (XV).

The compound of formula (XV) is reacted with a suitably substitutedcompound of formula (XIX), wherein PG² is a suitably selected nitrogenprotecting group, such as Boc, benzyl, Cbz, benzoyl, and the like, andwherein LG³ is a suitably selected leaving group such as Br, I, Cl,mesylate, tosylate, triflate, and the like, a known compound or compoundprepared by known methods; in the presence of a suitably selected base,such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selectedsolvent, such as DMF, DMP, THF, 1,4-doxane, and the like; to yield thecorresponding compound of formula (XXVI).

The compound of formula (XXVI) is de-protected according to knownmethods to yield the corresponding compound of formula (XVII). Forexample, wherein PG² is Boc, the compound of formula (XVI) isde-protected by reacting with a suitably selected acid, in a suitablyselected organic solvent, for example reacting with HCl in 1,4-dioxane,or reacting with TFA in DCM.

The compound of formula (XVII) is then further reacted with a suitablysubstituted compound of formula (XXII), a known compound or compoundprepared by known methods, as outlined in more detail in Scheme 1 above;to yield the corresponding compound of formula (I).

Compounds of formula (I) may alternatively be prepared according to theprocess as outlined in Scheme 3, below.

Accordingly, a suitably substituted compound of formula (XVIII),prepared for example as outlined in Scheme 1 above, is reacted with asuitably substituted compound of formula (XXVIII), wherein LG⁵ is asuitably selected leaving group, such as Cl, Br, I, mesylate, tosylatetriflate, and the like, a known compound or compound prepared asdescribed herein; in the presence of a suitably selected base, such asK₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent, suchas DMF, DMP, THF, 1,4-doxane, and the like; to yield the correspondingcompound of formula (XXIX).

The compound of formula (XXIX) is reacted with a suitably substitutedcompound of formula (XXIV), wherein the two R groups are each H, areeach the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— toform a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzukicoupling conditions, more particularly, in the presence of a suitablyselected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃,Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presenceof a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃,and the like; in a suitably selected solvent, such as DME, 1,4-dioxane,and the like, preferably mixed with water; to yield the correspondingcompound of formula (I).

Alternatively, a suitably substituted compound of formula (XXV),prepared for example, as described in Scheme 2 above, is reacted with asuitably substituted compound of formula (XVIII), prepared for exampleas outlined in Scheme 1 above, is reacted with a suitably substitutedcompound of formula (XXVIII), wherein LG⁵ is a suitably selected leavinggroup, such as Cl, Br, I, mesylate, tosylate, triflate, and the like, aknown compound or compound prepared as described herein; in the presenceof a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like;in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, andthe like; to yield the corresponding compound of formula (I).

The compound of formula (XXVIII) is a known compound or a compound thatmay be prepared, for example, according to the process outlined inScheme 4, below.

Accordingly, a suitably substituted compound of formula (XXX), a knowncompound or compound prepared by known methods (for example, byde-protecting the corresponding known, nitrogen-protected compound), isreacted with a suitably substituted compound of formula (XXII), a knowncompound or compound prepared by known methods, to yield thecorresponding compound of formula (XXIII), according to the process asoutlined in Scheme 1 above; to yield the corresponding compound offormula (XXXI).

The compound of formula (XXXI) is reacted with a suitably selectedsource of chlorine, such as POCl₃, SOCl₂, and the like; or suitablyselected source of bromine, such as PBr₃, POBr₃, CBr₄ in combinationwith PPh₃, and the like; or suitably selected source of iodine, such asI₂ in the presence of PPh₃; or suitably selected source of mesylate,such as MsCl, and the like; or other suitable selected source of anyother suitable LG⁵ leaving group; according to known methods; to yieldthe corresponding compound of formula (XXVIII).

Compounds of formula (XXV) may be prepared, for example, according tothe process outlined in Scheme 5, below.

Accordingly, a suitably substituted compound of formula (XV), preparedfor example as described in Scheme 1 above, is reacted with a suitablysubstituted compound of formula (XXXII), wherein LG⁶ wherein LG¹ is asuitably selected leaving group, such as Cl, Br, OH, and the like, toyield the corresponding compound of formula (XXXIII).

More particularly, wherein LG⁶ is Cl, Br, and the like, the compound offormula (XV) is reacted with the compound of formula (XXXII), in thepresence of a suitably selected organic base, such as pyridine, TEA,DIPEA, and the like; optionally in the presence of DMAP, and the like;in a suitably selected solvent such as DCM, DCE, THF, and the like.Alternatively, wherein LG⁶ is OH, and the like, the compound of formula(XV) is reacted with the compound of formula (XXXII), in the presence ofa suitably selected coupling reagent, such as HATU, HBTU, CDI, EDAC, andthe like, in the presence of a suitably selected organic base, such aspyridine, TEA, DIPEA, and the like; in a suitably selected organicsolvent, such as NMP, DMF, DCM, DCE, and the like.

The compound of formula (XXXIII) is reacted (to effect ring closure)with a suitably selected base, such as t-BuOK, NaOH, NaOCH₃, LHMDS, andthe like; in a suitably selected organic solvent or mixture of solvents,such as methanol, ethanol, water, 1,4-dioxane, and the like, and whereinthe base in LHMDS, in a suitably selected organic solvent, such as THF,and the like; to yield the corresponding compound of formula (XXV).

The compound of formula (XXV) is reacted with a suitably substitutedcompound of formula (XXVIII), wherein LG⁵ is a suitably selected leavinggroup, such as Cl, Br, I, mesylate, tosylate, triflate, and the like, aknown compound or compound prepared as described herein; in the presenceof a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like;in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, andthe like; to yield the corresponding compound of formula (I).

One skilled in the art will recognize that the compound of formula (XXV)may alternatively be reacted with a suitably substituted compound offormula (XIX), the product de-protected and then further reacted with asuitably substituted compound of formula (XXII), to yield thecorresponding compound of formula (I); as described in for, Scheme 1 orScheme 2, above; to yield the corresponding compound of formula (I).

The compound of formula (XXIV) is a known compound or compound preparedfor example, as described in Scheme 6, below.

Accordingly, a suitable substituted compound of formula (XXXIV), whereinQ² is hydrogen or a suitably selected oxygen protecting group, such asbenzyl, C₁₋₄alkyl (preferably methyl, ethyl, or t-butyl), and the like,and wherein LG⁷ is a suitably selected leaving group, such as Cl, Br, I,triflate, and the like, a known compound or compound prepared by knownmethods, is reacted with a suitably substituted compound of formula(XXIV), wherein the two R groups are each H, are each the same C₁₋₂alkylor are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e., to formthe

a known compound or compound prepared by known methods, under Suzukicoupling conditions, more particularly, in the presence of a suitablyselected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃,Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presenceof a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃,and the like; in a suitably selected solvent, such as DME, 1,4-dioxane,and the like, preferably mixed with water; to yield the correspondingcompound of formula (XXXV).

The compound of formula (XXXV) is reacted to yield the correspondingcompound of formula (XXXII). More particularly, wherein Q² is hydrogen,the compound of formula (XXXV) is reacted with a suitably selectedsource of chlorine, such as POCl₃, SOCl₂, and the like; or suitablyselected source of bromine, such as PBr₃, and the like; or suitablyselected source of iodine, such as I₂ in the presence of PPh₃; accordingto known methods; to yield the corresponding compound of formula (XXXII)wherein LG⁶ is chloro, bromo or iodo, respectively. Alternatively,wherein Q² is a suitably selected oxygen protecting group, for example,benzyl, the compound of formula (XXXV) is de-protected by hydrogenolysis(reacting with hydrogen in the presence of a Pd/C catalyst), accordingto known methods; according to known methods, to yield the correspondingcompound of formula (XXXII) wherein LG⁶ is OH. Alternatively still,wherein Q² is a suitably selected oxygen protecting group such ast-butyl, the compound of formula (XXXV) is de-protected by with asuitably selected acid, in a suitably selected organic solvent,according to known methods (e.g., with HCl in 1,4-dioxane or with TFA inDCM), to yield the corresponding compound of formula (XXXII) wherein LG⁶is OH. Alternatively still, wherein Q² is a suitably selected oxygenprotecting group, such as C₁₋₄alkyl, and the like, for example methyl orethyl, the compound of formula (XXXV) is de-protected by reacting with asuitably selected base, in a suitably selected mixture of water and anorganic solvent, according to known methods (for example reacting withNaOH or KOH in a mixture of water, THF and methanol), to yield thecorresponding compound of formula (XXXII), wherein LG⁶ is OH.

Compounds of formula (I) may alternatively be prepared according to theprocess outlined in Scheme 7, below.

Accordingly, a suitably substituted compound of formula (XXXVI), whereinQ³ is hydrogen or a suitably selected oxygen protecting group, such asbenzyl, C₁₋₄alkyl (preferably methyl, ethyl or t-butyl), and the like, aknown compound or compound prepared by known methods, is reacted with asuitably substituted compound of formula (XVI), wherein LG¹ is asuitably selected leaving group, such as Cl, Br, OH, and the like, andwherein LG² is a suitably selected leaving group, such as Cl, Br, OH,triflate, B(OH)₂, B(OC₁₋₂alkyl)₂,

and the like, a known compound or compound prepared by known methods;according to known methods, for example, according to the process asoutlined in Scheme 1 above; to yield the corresponding compound offormula (XXXVII), wherein Q⁴ is the corresponding LG² group.

Alternatively, a suitably substituted compound of formula (XXXVI),wherein Q³ is hydrogen or a suitably selected oxygen protecting groupsuch as benzyl, C₁₋₄alkyl (preferably methyl, ethyl or t-butyl), and thelike, a known compound or compound prepared by known methods; is reactedwith a suitably substituted compound of formula (XXXII), wherein LG⁶ isa suitably selected leaving group, such as Cl, Br, OH, and the like, aknown compound or compound prepared by known methods; according to knownmethods, for example, according to the process as outlined in Scheme 5above; to yield the corresponding compound of formula (XXXVII) whereinQ⁴ is R⁵.

The compound of formula (XXXVII) is then reacted to yield thecorresponding compound of formula (XXXVIII). More particularly, wherein

(a) Q³ is hydrogen, the compound of formula (XXXVII) is reacted withammonia or a suitably selected source of ammonia such as NH₄Cl, NH₄OH,gaseous NH₃, and the like; in the presence of a suitably selectedcoupling reagent, such as HATU, HBTU, CDI, EDAC, and the like, in thepresence of a suitably selected organic base, such as pyridine, TEA,DIPEA, and the like; in a suitably selected organic solvent, such asNMP, DMF, DCM, DCE, and the like; to yield the corresponding compound offormula (XXXVII);

(b) Q³ is a suitably selected oxygen protecting group, such as methyl,ethyl and the like, the compound of formula (XXXVII) is reacted withammonia or a suitably selected source of ammonia, such as concentratedNH₄OH, NH₄Cl, gaseous NH₃, and the like, according to known methods (forexample as described in (a) above), to yield the corresponding compoundof formula (XXXVIII);

or (c) wherein Q³ is a suitably selected oxygen protecting group, suchas benzyl, t-butyl, and the like, the compound of formula (XXXVII) isde-protected according to known methods (e.g., wherein Q² is benzyl,t-butyl and the like, by hydrogenolysis, reacting with hydrogen in thepresence of a catalyst such as Pd/C), or by reacting with a suitablyselected acid, in a suitably selected organic solvent (e.g., reactingwith HCl, in 1,4-dioxane or reacting with TFA in DCM) to yield thecorresponding compound of formula (XXXVII) wherein Q³ is hydrogen; suchcompound is then reacted with ammonia or a suitably selected source ofammonia as described in (a) above, to yield the corresponding compoundof formula (XXXVIII).

The compound of formula (XXXVIII) is reacted (to effect ring closure)with a suitably selected base, such as t-BuOK, NaOH, NaOCH₃, LHMDS, andthe like; in a suitably selected organic solvent or mixture of solvents,such as methanol, ethanol, water, 1,4-dioxane, and the like, and whereinthe base in LHMDS, in a suitably selected organic solvent, such as THF,and the like; to yield the corresponding compound of formula (XXXIX).

The compound of formula (XXXIX) is reacted, according to the proceduresas described herein, to yield the desired compound of formula (I). Forexample, the compound of formula (XXXIX), wherein Q⁴ is a suitablyelected leaving group, may be substituted for the compound of formula(XVIII) in Scheme 1 reacted according to the procedure as described inScheme 1, to yield the desired compound of formula (I). Alternatively,the compound of formula (XXXIX), wherein Q⁴ is R⁵, may be substitutedfor the compound of formula (XV) in Scheme 2 or the compound of formula(XXV) in Scheme 3, and reacted as described therein, respectively, toyield the corresponding compound of formula (I).

Compounds of formula (l), wherein R¹ and R² are taken together with thecarbon atom to which they are bound to form an optionally substituted 4to 8-membered, saturated heterocyclyl of the formula

wherein p and q are each independently selected to be an integer from 0to 2, and wherein the “⋅” denotes the carbon atom of the spiroattachment to the imidazolidin-5-one core, may alternatively prepared asdescribed in Scheme 8, below.

Accordingly, a suitably substituted compound of formula (XL) wherein PG⁴is a suitably selected nitrogen protecting group, such as Boc, Cbz,benzyl, and the like, wherein Q⁴ is —R⁵ or a suitably selected leavinggroup, such as Cl, Br, I, OH, and the like, and wherein Q⁵ is -L¹-R³ ora suitably selected nitrogen protecting group such as Boc, benzyl, Cbz,and the like; and wherein Q⁵ is a nitrogen protecting group, thenpreferably, PG⁴ and the Q⁵ nitrogen protecting group are selected suchthat the two nitrogen protecting groups are removed under differentconditions (i.e., the two nitrogen protecting groups are different andare selected such that each may be selectively removed without removingthe other), a known compound or compound prepared by known methods, forexample, as described in Scheme 1 above, is de-protected to remove thePG⁴ group, according to known methods, to yield the correspondingcompound of formula (XLI). For example, wherein PG⁴ is Boc, the compoundof formula (XL) may be de-protected by reacting with a suitably selectedacid, such as HCl, and the like, in a suitably selected organic solvent,such as 1,4-dioxane, and the like.

The compound of formula (XLI) is then reacted to yield the correspondingcompound of formula (I). Wherein the compound of formula (XLI) Q⁴ is —R⁵and Q⁵ is -L¹-R³, then the compound of formula (XLI) is reacted with asuitably selected compound of formula (XLII), wherein LG⁸ is OH or asuitably selected leaving group, such as Cl, Br, mesylate, tosylate, andthe like, a known compound or compound prepared by known methods,according to known methods readily recognized by those skilled in theart, e.g., alkylation, peptide coupling, and the like, to yield thecorresponding compound of formula (I). Alternatively, the compound offormula (XLI) may be reacted with a suitably selected compound offormula (XLII) wherein LG⁵ includes an aldehyde or ketone carbonylgroup, as would be readily recognized by one skilled in the art, underreductive amination conditions as known in the art, (for example,reacting with sodium triacetoxyborohydride and acetic acid, in asuitably selected solvent, such as DCM, DCE, THF, and the like; orreacting with cyanoborohydride in a suitably selected solvent, such asmethanol, and the like), to yield the corresponding compound of formula(I).

Wherein the compound of formula (XLI) Q⁴ is a suitably selected leavinggroup and/or Q⁵ is a suitably selected nitrogen protecting group, thenthe compound of formula (XLI) may alternatively be reacted to: (a)attach the R⁵ group by reacting with, for example, a suitablysubstituted compound of formula (XXIV), as described in, for example,Scheme 1, above; (b) remove of the Q⁵ nitrogen protecting group and thenattach the -L¹-R³ group by reacting with, for example, a suitablysubstituted compound of formula (XXII), as described in, for example,Scheme 1 above; and (c) attach the —R¹⁰ group, as described above; inany order or sequence; to yield the corresponding compound of formula(I).

One skilled in the art will recognize that the compounds of formula (I)of the present invention may be prepared according to the methods asdescribed herein, or alternatively by attaching substituent groups, suchas

R¹⁰, etc., and effecting ring closure to form the imidazolidin-4-onering core, in any order or sequence, protecting and de-protectingreactive groups, as necessary or desirable, according to methods asdescribed herein or known to those skilled in the art. One skilled inthe art will further recognize that some such sequences may result inreaction steps with better reactivity profiles, yields and/orselectivity, and thus may be more efficient or desirable than otherroutes.

One skilled in the art will further recognize that when any of thecoupling steps described above a reactant is substituted with a suitablyselected leaving group, such as OH, triflate, and the like, suchcoupling may alternatively be effected by converting the leaving groupto a group of the formula —B(OR)₂, wherein the two R groups are each H,are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂—to form a ring (i.e., to form the

and then completing the coupling under Suzuki coupling conditions, asherein described and known to those skilled in the art.

The present invention further comprises pharmaceutical compositionscontaining one or more compounds of formula (I) with a pharmaceuticallyacceptable carrier. Pharmaceutical compositions containing one or moreof the compounds of the invention described herein as an activeingredient can be prepared by intimately mixing the compound orcompounds with a pharmaceutical carrier according to conventionalpharmaceutical compounding techniques. The carrier may take a widevariety of forms depending upon the desired route of administration(e.g., oral, parenteral). Thus, for liquid oral preparations, such assuspensions, elixirs and solutions, suitable carriers and additivesinclude water, glycols, oils, alcohols, flavoring agents, preservatives,stabilizers, coloring agents and the like; for solid oral preparations,such as powders, capsules, and tablets, suitable carriers and additivesinclude starches, sugars, diluents, granulating agents, lubricants,binders, disintegrating agents and the like. Solid oral preparations mayalso be coated with substances such as sugars or be enteric-coated so asto modulate major site of absorption. For parenteral administration, thecarrier will usually include sterile water and other ingredients may beadded to increase solubility or preservation. Injectable suspensions orsolutions may also be prepared utilizing aqueous carriers along withappropriate additives.

To prepare the pharmaceutical compositions of this invention, one ormore compounds of the present invention as an active ingredient isintimately admixed with a pharmaceutical carrier according toconventional pharmaceutical compounding techniques, such carrier maytake a wide variety of forms depending of the form of preparationdesired for administration, e.g., oral or parenteral such asintramuscular. In preparing the compositions in oral dosage form, any ofthe usual pharmaceutical media may be employed. Thus, for liquid oralpreparations, such as, for example, suspensions, elixirs and solutions,suitable carriers and additives include water, glycols, oils, alcohols,flavoring agents, preservatives, coloring agents and the like; for solidoral preparations such as, for example, powders, capsules, caplets,gelcaps and tablets, suitable carriers and additives include starches,sugars, diluents, granulating agents, lubricants, binders,disintegrating agents and the like. Because of their ease inadministration, tablets and capsules represent the most advantageousoral dosage unit form, in which case solid pharmaceutical carriers areobviously employed. If desired, tablets may be sugar coated or entericcoated by standard techniques. For parenterals, the carrier will usuallyinclude sterile water, through other ingredients, for example, forpurposes such as aiding solubility or for preservation, may be included.Injectable suspensions may also be prepared, in which case appropriateliquid carriers, suspending agents and the like may be employed. Thepharmaceutical compositions herein will contain, per dosage unit, e.g.,tablet, capsule, powder, injection, teaspoonful and the like, an amountof the active ingredient necessary to deliver an effective dose asdescribed above. The pharmaceutical compositions herein will contain,per unit dosage unit, e.g., tablet, capsule, powder, injection,suppository, teaspoonful and the like, of from about 0.01 mg to about1000 mg or any amount or range therein, and may be given at a dosage offrom about 0.01 mg/kg/day to about 300 mg/kg/day, or any amount or rangetherein, preferably from about 0.1 mg/kg/day to about 100 mg/kg/day, orany amount or range therein, preferably from about 0.50 mg/kg/day toabout 50 mg/kg/day, or any amount or range therein, preferably fromabout 0.75 mg/kg/day to about 15 mg/kgiday, or any amount or rangetherein, preferably from about 1.0 mg/kg/day to about 7.5 mg/kg/day, orany amount or range therein, preferably from about 1.5 mg/kg/day toabout 5.0 mg/kg/day, or any amount or range therein. The dosages,however, may be varied depending upon the requirement of the patients,the severity of the condition being treated and the compound beingemployed. The use of either daily administration or post-periodic dosingmay be employed.

Preferably these compositions are in unit dosage forms, such as tablets,pills, capsules, powders, granules, sterile parenteral solutions orsuspensions, metered aerosol or liquid sprays, drops, ampoules,autoinjector devices or suppositories; for oral parenteral, intranasal,sublingual or rectal administration, or for administration by inhalationor insufflation. Alternatively, the composition may be presented in aform suitable for once-weekly or once-monthly administration; forexample, an insoluble salt of the active compound, such as the decanoatesalt, may be adapted to provide a depot preparation for intramuscularinjection. For preparing solid compositions, such as tablets, theprincipal active ingredient(s) is mixed with a pharmaceutical carrier,e.g., conventional tableting ingredients, such as corn starch, lactose,sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalciumphosphate or gums, and other pharmaceutical diluents, e.g., water, toform a solid preformulation composition containing a homogeneous mixtureof a compound of the present invention, or a pharmaceutically acceptablesalt thereof. When referring to these preformulation compositions ashomogeneous, it is meant that the active ingredient is dispersed evenlythroughout the composition so that the composition may be readilysubdivided into equally effective dosage forms such as tablets, pillsand capsules. This solid preformulation composition is then subdividedinto unit dosage forms of the type described above containing from about0.01 mg to about 1,000 mg, or any amount or range therein, of the activeingredient of the present invention. The tablets or pills of the novelcomposition can be coated or otherwise compounded to provide a dosageform affording the advantage of prolonged action. For example, thetablet or pill can comprise an inner dosage and an outer dosagecomponent, the latter being in the form of an envelope over the former.The two components can be separated by an enteric layer which serves toresist disintegration in the stomach and permits the inner component topass intact into the duodenum or to be delayed in release. A variety ofmaterials can be used for such enteric layers or coatings, suchmaterials include a number of polymeric acids with materials, such asshellac, cetyl alcohol and cellulose acetate.

The liquid forms in which the compositions of the present invention maybe incorporated for administration orally or by injection include,aqueous solutions, suitably flavoured syrups, aqueous or oilsuspensions, and flavoured emulsions with edible oils such as cottonseedoil, sesame oil, coconut oil or peanut oil, as well as elixirs andsimilar pharmaceutical vehicles. Suitable dispersing or suspendingagents for aqueous suspensions, include synthetic and natural gums, suchas tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose,methylcellulose, polyvinyl-pyrrolidone or gelatin.

The method of treating disorders described in the present invention mayalso be carried out using a pharmaceutical composition including any ofthe compounds as defined herein and a pharmaceutically acceptablecarrier. The pharmaceutical composition may contain between about 0.01mg and about 1000 mg of the compound, or any amount or range therein;preferably from about 1.0 mg to about 500 mg of the compound, or anyamount or range therein, and may be constituted into any form suitablefor the mode of administration selected. Carriers include necessary andinert pharmaceutical excipients, including, but not limited to, binders,suspending agents, lubricants, flavorants, sweeteners, preservatives,dyes, and coatings. Compositions suitable for oral administrationinclude solid forms, such as pills, tablets, caplets, capsules (eachincluding immediate release, timed release and sustained releaseformulations), granules, and powders, and liquid forms, such assolutions, syrups, elixers, emulsions, and suspensions. Forms useful forparenteral administration include sterile solutions, emulsions andsuspensions.

Advantageously, compounds of the present invention may be administeredin a single daily dose, or the total daily dosage may be administered individed doses of two, three or four times daily. Furthermore, compoundsfor the present invention can be administered in intranasal form viatopical use of suitable intranasal vehicles, or via transdermal skinpatches well known to those of ordinary skill in that art. To beadministered in the form of a transdermal delivery system, the dosageadministration will, of course, be continuous rather than intermittentthroughout the dosage regimen.

For instance, for oral administration in the form of a tablet orcapsule, the active drug component can be combined with an oral,pharmaceutically acceptable inert carrier, such as ethanol, glycerol,water and the like. Moreover, when desired or necessary, suitablebinders; lubricants, disintegrating agents and coloring agents can alsobe incorporated into the mixture. Suitable binders include, withoutlimitation, starch, gelatin, natural sugars, such as glucose orbeta-lactose, corn sweeteners, natural and synthetic gums, such asacacia, tragacanth or sodium oleate, sodium stearate, magnesiumstearate, sodium benzoate, sodium acetate, sodium chloride, and thelike. Disintegrators include, without limitation, starch, methylcellulose, agar, bentonite, xanthan gum and the like.

The liquid forms in suitably flavored suspending or dispersing agentssuch as the synthetic and natural gums, e.g., tragacanth, acacia,methyl-cellulose and the like. For parenteral administration, sterilesuspensions and solutions are desired. Isotonic preparations thatgenerally contain suitable preservatives are employed when intravenousadministration is desired.

To prepare a pharmaceutical composition of the present invention, acompound of formula (I) as the active ingredient is intimately admixedwith a pharmaceutical carrier according to conventional pharmaceuticalcompounding techniques, which carrier may take a wide variety of formsdepending of the form of preparation desired for administration (e.g.,oral or parenteral). Suitable pharmaceutically acceptable carriers arewell known in the art. Descriptions of some of these pharmaceuticallyacceptable carriers may be found in The Handbook of PharmaceuticalExcipients, published by the American Pharmaceutical Association and thePharmaceutical Society of Great Britain.

Methods of formulating pharmaceutical compositions have been describedin numerous publications such as Pharmaceutical Dosage Forms: Tablets,Second Edition, Revised and Expanded, Volumes 1-3, edited by Liebermanet al; Pharmaceutical Dosage Forms: Parenteral Medications, Volumes 1-2,edited by Avis et al; and Pharmaceutical Dosage Forms: Disperse Systems,Volumes 1-2, edited by Lieberman et al; published by Marcel Dekker, Inc.

Compounds of this invention may be administered in any of the foregoingcompositions and according to dosage regimens established in the artwhenever treatment of disorders mediated by inhibition of fatty acidsynthase (FASN) enzyme, as described herein, is required.

The daily dosage of the products may be varied over a wide range fromabout 0.01 mg to about 1,000 mg per adult human per day, or any amountor range therein. For oral administration, the compositions arepreferably provided in the form of tablets containing about 0.01, 0.05,0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 150, 200, 250, 500and 1000 milligrams of the active ingredient each for the symptomaticadjustment of the dosage to the patient to be treated. An effectiveamount of the drug is ordinarily supplied at a dosage level of fromabout 0.01 mg/kg to about 300 mg/kg of body weight per day, or anyamount or range therein. Preferably, the range is from about 0.5 toabout 50.0 mg/kg of body weight per day, or any amount or range therein.More preferably, from about 0.75 to about 15.0 mg/kg of body weight perday, or any amount or range therein. More preferably, from about 1.0 toabout 7.5 mg/kg of body weight per day, or any amount or range therein.The compounds may be administered on a regimen of 1 to 4 times per day.

Optimal dosages to be administered may be readily determined by thoseskilled in the art, and will vary with the particular compound used, themode of administration, the strength of the preparation, the mode ofadministration, and the advancement of the disease condition. Inaddition, factors associated with the particular patient being treated,including patient age, weight, diet and time of administration, willresult in the need to adjust dosages.

One skilled in the art will recognize that, both in vivo and in vitrotrials using suitable, known and generally accepted cell and/or animalmodels are predictive of the ability of a test compound to treat orprevent a given disorder.

One skilled in the art will further recognize that human clinical trailsincluding first-in-human, dose ranging and efficacy trials, in healthypatients and/or those suffering from a given disorder, may be completedaccording to methods well known in the clinical and medical arts.

The following Examples are set forth to aid in the understanding of theinvention, and are not intended and should not be construed to limit inany way the invention set forth in the claims that follow thereafter.

SYNTHESIS EXAMPLES

In the following Examples, some synthesis products are listed as havingbeen isolated as a residue. It will be understood by one of ordinaryskill in the art that the term “residue” does not limit the physicalstate in which the product was isolated and may include, for example, asolid, an oil, a foam, a gum, a syrup, and the like.

Example 12-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl-}3-diazaspiro[4.4]non-1-en-4-one(Compound #2)

STEP A: 4-Bromo-N-(1-carbamoylcyclopentyl)benzamide

A mixture 1-aminocyclopentanecarboxamide (0.5 g, 3.9 mmol),4-bromobenzoic acid (0.784 g, 3.9 mmol), EDCI (0.747 g, 3.9 mmol), HOBt(0.527 g, 3.9 mmol) and DIEA (0.67 mL, 3.9 mmol) in DMF (10 mL) wasstirred at room temperature for 1 day. The reaction mixture waspartitioned between EtOAc and aqueous saturated NaHCO₃. The organicphase was washed with brine, dried over Na₂SO₄, filtered andconcentrated in vacuo to yield4-bromo-N-(1-carbamoylcyclopentyl)benzamide (1.2 g, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.54-1.82 (m, 3H), 1.89-2.04 (m, 2H),2.04-2.23 (m, 2H), 6.76 (br. s., 1H), 7.09 (br. s., 1H), 7.66 (d, J=8.6Hz, 2H), 7.83 (d, J=8.6 Hz, 2H), 8.36 (s, 1H); MS m/z 313.0 (M+H)⁺.

STEP B: 2-(4-Bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one

A mixture of 4-bromo-N-(1-carbamoylcyclopentyl)benzamide (1.0 g, 3.21mmol) and NaOH (0.64 g, 16.06 mmol) in H₂O (3.25 mL) and MeOH (50 mL)was stirred at 65° C. for 1 day. The reaction mixture was partitionedbetween water (300 mL) and EtOAc (300 mL). The organic phase was washedwith brine, dried over Na₂SO₄, filtered and concentrated in vacuo toyield 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (0.9 g, 95%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.69-1.79 (m, 2H), 1.80-1.92 (m, 6H),5.76 (s, 1H), 7.74 (d, J=8.3 Hz, 2H), 7.90 (d. J=7.6 Hz, 2H); MS m/z295.0 (M+H)⁺.

STEP C: (S)-ter-Butyl3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate

To a stirring solution of2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (50 mg, 0.17 mmol)and (R)-tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate (90.1 mg,0.34 mmol) in DMF (3 mL) was added Cs₂CO₃ (139 mg, 0.42 mmol). Afterstirring at room temperature for 1 h and 65° C. for 17 h, the reactionmixture was partitioned between aqueous NaHCO₃ and EtOAc. The organicphase was washed with brine, dried over Na₂SO₄, filtered andconcentrated in vacuo to yield a residue. The residue was purified byflash chromatography (silica gel, 40% EtOAc/heptane) to yield(S)-ter-butyl3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate(62 mg, 76%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.42 (s, 9H), 1.74-1.82 (m, 1H), 1.82-1.91(m, 2H), 1.91-2.10 (m, 7H), 2.24 (dt, J=14.7, 7.4 Hz, 1H), 2.73-2.89 (m,1H), 3.11-3.40 (m, 3H), 3.49-3.68 (m, 2H), 7.45 (d, J=8.6 Hz, 2H), 7.64(d, J=8.1 Hz, 2H); MS m/z 476.1 (M+H)⁺.

STEP D:(R)-2-(4-Bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of (S)-tert-butyl3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate(270 mg, 0.56 mmol) in 1,4-dioxane was added 4M HCl in 1,4-dioxane (17mL). After stirring overnight at room temperature the reaction mixturewas concentrated to yield(R)-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one,as its corresponding HCl salt, as a solid, which was directly used intothe next step; MS m/z 376 (M+H)⁺.

STEP E:(R)-2-(4-Bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of(R)-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-oneHOC salt (234 mg, 0.56 mmol) in DCM (15 mL) and DIPEA (0.21 mL, 1.25mmol) was added cyclopropanecarbonyl chloride (0.053 mL, 0.56 mmol).After stirring at room temperature for 3 h, the reaction mixture waspartitioned between aqueous NaHCO₃ and DCM. The organic phase was washedwith brine, dried over Na₂SO₄, filtered and concentrated in vacuo toyield(R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(250 mg, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.58-0.74 (m, 4H), 1.40-1.64 (m, 1H),1.68 (td, J=12.0, 6.8 Hz, 1H), 1.73-1.83 (m, 3H), 1.88 (br. s., 6H),2.04-2.14 (m, 1H), 2.80 (dd, J=11.6, 7.1 Hz, 1H), 3.03-3.14 (m, 1H),3.17-3.28 (m, 1H), 3.38-3.55 (m, 2H), 3.58 (t, J=8.1 Hz, 2H), 7.60-7.68(m, 2H), 7.71-7.78 (m, 2H); MS m/z 444.1 (M+H)⁺.

STEP F:(R)-2-(4-(Benzofuran-5-ylphenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one,Compound #2

To a solution of(R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(150 mg, 0.338 mmol) and benzofuran-5-ylboronic acid (86.32 mg, 0.506mol) in DME (3 mL) was added under argon aqueous 2M Na₂CO₃ (0.35 mL,0.709 mmol) and Pd(PPh₃)₄ (15 mg, 0.013 mmol). The reaction mixture wasrefluxed for 16 h, filtered and concentrated in vacuo and the resultingresidue was purified by preparative reverse-phase chromatography toyield(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(80 mg, 49%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.66-0.77 (m, 2H), 0.86-1.01 (m, 2H),1.23-1.75 (m, 3H), 1.78-2.17 (m, 9H), 2.28-2.56 (m, 1H), 2.99-3.25 (m,1H), 3.26-3.57 (m, 2H), 3.57-3.82 (m, 3H), 6.85 (s, 1H), 7.56 (d, 1H),7.61 (d, 1H), 7.64-7.71 (m, 3H), 7.73-7.80 (m, 2H), 7.84 (s, 1H); MS m/z482.3 (M+H)⁺.

Following the procedure described in Example 1, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the followingintermediate compounds were prepared:

Following the procedure described in Example 1, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  75

1-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)piperidin-4-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.70 (dd, J = 7.8, 3.2 Hz, 2 H), 0.87-0.95 (m, 2 H), 0.95-1.02 (m, 1H), 1.02-1.17 (m, 1 H), 1.40-1.62 (m, 2 H), 1.63-1.72 (m, 1 H),1.73-1.84 (m, 2 H), 1.85-2.15 (m, 8 H), 2.47 (t, J = 11.7 Hz, 1 H), 2.97(t, J = 12.5 Hz, 1 H), 3.57 (dd, J = 15.7, 7.1 Hz, 2 H), 4.07-4.22 (m, 1H), 4.51 (d, J = 12.2 Hz, 1 H), 6.85 (d, J = 2.0 Hz, 1 H), 7.52-7.60 (m,2 H), 7.62-7.66 (m, 2 H), 7.69 (d, J = 2.2 Hz, 1 H), 7.75 (d, J = 8.3Hz, 2 H), 7.85 (s, 1 H); MS m/z 496.2 (M + H)⁺.  76

3-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.71 (dd, J= 7.8, 3.2 Hz, 2 H), 0.83-0.96 (m, 2 H), 0.96-1.03 (m, 1 H), 1.03-1.19(m, 1 H), 1.47 (br. s., 1 H), 1.56 (br. s., 1 H), 1.62-1.72 (m, 1 H),1.72-1.86 (m, 2 H), 1.87-2.16 (m, 9 H), 2.46 (t, J =12.2 Hz, 1 H), 2.96(t, J = 12.0 Hz, 1 H), 3.58 (dd, J = 9.8, 8.1 Hz, 2 H), 4.50 (br. s., 1H), 6.63 (br. s., 1 H), 7.26 (br. s., 1 H), 7.43-7.52 (m, 2 H), 7.62 (d,J = 8.3 Hz, 2 H), 7.78 (d, J = 8.1 Hz, 2 H), 7.92 (s, 1 H), 8.61 (br.s., 1 H); MS m/z 495.3 (M + H)⁺  77

3-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.62- 0.77(m, 2 H), 0.85-1.03 (m, 3 H), 1.03- 1.16 (m, 1 H), 1.41-1.63 (m, 2 H),1.63- 1.71 (m, 1 H), 1.81 (m, J = 11.3, 7.5, 3.8, 3.8 Hz, 1 H),1.88-2.17 (m, 8 H), 2.46 (t, J = 11.5 Hz, 1 H), 2.97 (t, J = 12.5 Hz, 1H), 3.50-3.70 (m, 2 H), 4.04-4.23 (m, 1 H), 4.50 (d, J = 12.0 Hz, 1 H),7.63-7.77 (m, 3 H), 7.81-7.95 (m, 3 H), 8.03-8.15 (m, 2 H), 8.59 (d, J =5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 507.3 (M + H)⁺  78

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (dd, J7.6, 3.5 Hz, 2 H), 0.92-1.03 (m, 2 H), 1.24-1.38 (m, 1 H), 1.96-2.25 (m,6 H), 2.25-2.39 (m, 2 H), 2.80-2.98 (m, 1 H), 3.70 (br. s., 1 H),3.85-4.41 (m, 5 H), 6.65 (br. s., 1 H), 7.30 (br. s., 1 H), 7.45 (d, 1H), 7.50 (d, J = 8.1 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 2 H), 7.88 (d, J =8.1 Hz, 2 H), 7.93 (s, 1 H), 8.52 (br. s., 2 H); MS m/z 467.0 (M + H)⁺ 79

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70 (dd, J7.3, 3.8 Hz, 2 H), 0.84-0.96 (m, 2 H), 1.23-1.34 (m, 1 H), 1.71-2.16 (m,10 H), 2.70-2.84 (m, 1 H), 3.57 (dd, J = 9.9, 5.8 Hz, 1 H), 3.82-4.05(m, 4 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.75 (d, J = 6.1 Hz, 1 H), 7.88 (d,J = 8.1 Hz, 2 H), 7.91 (d, 1 H), 8.07 (s, 1 H), 8.12 (d, J = 8.6 Hz, 1H), 8.60 (d, J = 5.6 Hz, 1 H), 9.33 (s, 1 H); MS m/z 478.9 (M + H)⁺  80

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77(dd, J = 7.3, 3.3 Hz, 2 H), 0.88-1.03 (m, 2 H), 1.21-1.38 (m, 1 H),1.99-2.29 (m, 8 H), 2.79-2.98 (m, 1 H), 3.68 (br. s., 1 H), 3.90-4.23(m, 4 H), 4.24-4.41 (m, 1 H), 6.87 (s, 1 H), 7.57 (d, J = 8.6 Hz, 1 H),7.63 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.5 Hz, 1 H), 7.75-7.83 (m, 2H), 7.84-7.92 (m, 3 H); MS m/z 468.0 (M + H)⁺  74

3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-yl-2-methylphenyl)-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz,DMSO-d₆) δ ppm 0.56- 0.68 (m, 4 H), 1.27-1.66 (m, 2 H), 1.69- 1.98 (m, 9H), 2.10-2.34 (m, 1 H), 2.39 (s, 3 H), 2.74-3.32 (m, 3 H), 3.36-3.59 (m,3 H), 7.62 (dd, J = 18.4, 7.8 Hz, 1 H), 7.81- 7.88 (m, 1 H), 7.91 (d, J= 5.6 Hz, 2 H), 8.10 (d, J = 8.6 Hz, 1 H), 8.25 (d, J = 8.6 Hz, 1 H),8.38 (s, 1 H), 8.55 (d, J = 5.6 Hz, 1 H), 9.37 (s, 1 H); MS m/z 506.9(M + H)⁺  1

4′-(3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4-oxo-1,3-diazaspiro[4.4]non-1-en-2-yl)biphenyl-4-carbonitrile ¹H NMR (400 MHz, CDCl₃) δ ppm 0.64- 0.78(m, 2 H), 0.86-1.01 (m, 2 H), 1.39- 1.88 (m, 3 H), 1.88-2.15 (m, 8 H),2.25- 2.54 (m, 1 H), 2.92-3.27 (m, m1 H), 3.27- 3.58 (m, 2 H), 3.58-3.83(m, 3 H), 7.69- 7.82 (m, 8 H); MS m/z 467.3 (M + H)⁺  66

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-5-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.68- 0.78(m, 2 H), 0.88-1.03 (m, 2 H), 1.42- 2.01 (m, 6 H), 2.02-2.16 (m, 4 H),2.34- 2.61 (m, 1 H), 2.99-3.61 (m, 3 H), 3.62- 3.84 (m, 3 H), 7.36-7.44(m, 1 H), 7.55 (d, J = 7.1 Hz, 1 H), 7.59-7.67 (m, 2 H), 7.70- 7.77 (m,2 H), 7.80 (t, J = 7.8 Hz, 1 H), 8.19 (dt, J = 8.5, 4.6 Hz, 2 H), 8.97(d, J = 4.0 Hz, 1 H); MS m/z 493.2 (M + H)⁺  67

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-5-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.73(dd, J = 7.8, 3.3 Hz, 2 H), 0.88-1.03 (m, 2 H), 1.44-1.76 (m, 2 H),1.76-2.18 (m, 9 H), 2.34-2.62 (m, 1 H), 2.99-3.31 (m, 1 H), 3.31-3.62(m, 2 H), 3.62-3.85 (m, 3 H), 7.61-7.78 (m, 7 H), 8.02-8.10 (m, 1 H),8.53 (dd, J = 5.8, 2.8 Hz, 1 H), 9.35 (s, 1 H); MS m/z 493.2 (M + H)⁺ 68

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-4-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.76(dd, J = 7.8, 2.8 Hz, 2 H), 0.98 (d, J = 4.5 Hz, 2 H), 1.41-1.75 (m, 2H), 1.88-2.38 (m, 9 H), 2.41-2.66 (m, 1 H), 3.10-3.33 (m, ,1 H), 3.60(d, 3 H), 3.86-4.00 (m, 2 H), 6.68 (br. s., 1 H), 7.23 (d, 1 H), 7.30(d, 1 H), 7.32 (d, J = 3.0 Hz, 1 H), 7.48 (d, J = 8.1 Hz, 1 H), 7.83 (d,J = 8.6 Hz, 2 H), 7.94 (d, J = 8.1 Hz, 2 H), 8.53 (br. s., 1 H); MS m/z481.2 (M + H)⁺  69

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-7-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.65-0.80 (m, 2 H), 0.86-1.03 (m, 2 H), 1.43- 2.17 (m, 11 H), 2.28-2.55 (m, 1H), 2.96- 3.58 (m, 3 H), 3.59-3.83 (m, 3 H), 7.70- 7.78 (m, 3 H),k7.82-7.91 (m, 2 H), 7.93- 8.04 (m, 2 H), 8.23 (s, 1 H), 8.58 (d, J = 6.1Hz, 1 H), 9.37 (s, 1 H); MS m/z 493.2 (M + H)⁺  70

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrrolidin-3-yl]methyl}-2-[3′-(1H-pyrazol-3-yl)biphenyl-4-yl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz,CDCl₃) δ ppm 0.77 (d, J = 6.6 Hz, 2 H), 0.90-1.04 (m, 2 H), 1.41- 1.76(m, 2 H), 1.86-2.17 (m, 5 H), 2.17- 2.36 (m, 4 H), 2.38-2.70 (m, 1 H),2.98- 3.64 (m, 3 H), 3.64-4.00 (m, 3 H), 6.83 (d, J = 2.5 Hz, 1 H), 7.59(t, J = 7.8 Hz, 1 H), 7.68 (d, J = 7.6 Hz, 1 H), 7.77 (d, J = 7.6 Hz, 1H), 7.81-7.91 (m, 5 H), 7.96-8.05 (m, 1 H); MS m/z 508.3 (M + H)⁺  11

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-6-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.57- 0.70(m, 4 H), 1.35-1.70 (m, 2 H), 1.71- 2.14 (m, 26 H), 2.21-2.45 (m, 1 H),2.83- 3.52 (m, 3 H), 3.52-3.67 (m, 1 H), 3.77 (t, J = 8.8 Hz, 2 H), 7.92(dd, J = 8.1, 4.5 Hz, 1 H), 8.01 (t, J = 7.3 Hz, 2 H), 8.18 (dd, J =7.8, 4.3 Hz, 2 H), 8.33-8.40 (m, 1 H), 8.41- 8.48 (m, 1 H), 8.69 (s, 1H), 8.91 (d, J = 8.1 Hz, 1 H), 9.18 (d, J = 3.5 Hz, 1 H); MS m/z 493.3(M + H)⁺  12

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.64(d, J = 5.1 Hz, 4 H), 1.31-1.74 (m, 2 H), 1.74-2.16 (m, 9 H), 2.19-2.45(m, 1 H), 2.82-3.51 (m, 3 H), 3.52-3.67 (m, 1 H), 3.69-3.83 (m, 2 H),8.05 (t, J = 8.1 Hz, 2 H), 8.24 (dd, J = 8.1, 5.1 Hz, 2 H), 8.47 (d, J =8.6 Hz, 1 H), 8.53 (d, J = 6.6 Hz, 1 H), 8.67 (d, J = 9.1 Hz, 1 H), 8.73(d, J = 6.6 Hz, 1 H), 8.80 (s, 1 H), 9.94 (s, 1 H); MS m/z 493.3 (M +H)⁺  13

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 446.3 (M + H)⁺  72

2-[4-(1-Benzofuran-5-yl)-2-methylphenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃)δ ppm 0.72- 0.85 (m, 2 H), 0.93-1.07 (m, 2 H), 1.42- 1.70 (m, 2 H),1.84-2.35 (m, 9 H), 2.38- 2.61 (m, 1 H), 2.43 (s, 3 H), 2.98-3.26 (m, 1H), 3.31-3.75 (m, 5 H), 6.86 (s, 1 H), 7.41-8.08 (m, 11 H); MS m/z 495.9(M + H)⁺  73

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)-2-methylphenyl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, CDCl₃)δ ppm 0.77 (d, J = 7.6 Hz, 2 H), 0.92-1.07 (m, 2 H), 1.42- 1.68 (m, 2H), 1.83-2.17 (m, 5 H), 2.18- 2.38 (m, 4 H), 2.42 (s, 3 H), 2.44-2.61(m, 1 H), 3.00-3.25 (m, 1 H), 3.30-3.75 (m, 5 H), 6.63 (br. s., 1 H),7.29 (br. s., 1 H), 7.39-7.52 (m, 3 H), 7.61-7.70 (m, 2 H), 7.90 (s, 1H), 8.45 (br. s., 1 H); MS m/z 495.0 (M + H)⁺  93

2-(4′-Chloro-3-methylbiphenyl-4-yl)-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.71- 0.85 (m, 2 H), 0.92-1.07 (m, 2 H), 1.39- 1.71 (m, 2 H),1.82-2.31 (m, 8 H), 2.33- 2.59 (m, 1 H), 2.42 (s, 3 H), 2.95-3.27 (m, 1H), 3.30-3.74 (m, 5 H), 7.43-7.52 (m, 3 H), 7.56 (d, J = 9.1 Hz, 4 H);MS m/z 489.9 (M + H)⁺  3

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-pyridin-4-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-oneMS m/z 443.2 (M + H)⁺  4

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.78(dd, J 7.6, 3.0 Hz, 2 H), 0.90-1.06 (m, 2 H), 1.39-1.76 (m, 2 H),1.84-2.67 (m, 10 H), 3.06-3.78 (m, 4 H), 3.84-4.02 (m, 2 H), 6.64 (br.s., 1 H), 7.29 (br. s., 1 H), 7.41-7.52 (m, 2 H), 7.76-7.82 (m, 2 H),7.83-7.90 (m, 2 H), 7.93 (s, 1 H), 8.51- 8.62 (m, 1 H); MS m/z 481.3(M + H)⁺  5

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-pyridin-3-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-oneMS m/z 443.2 (M + H)⁺  22

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-03-yl]methyl}-2-(4-quyinolin-4-ylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 493.3 (M + H)⁺  82

2-(4′-Chlorobiphenyl-4-yl)-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.70- 0.86 (m, 2 H), 0.98 (br. s., 2 H), 1.41-2.33 (m, 10 H),2.35-2.64 (m, 1 H), 3.03-3.32 (m, 1 H), 3.32-3.63 (m, 2 H), 3.63-3.76(m, 1 H), 3.77-3.94 (m, 2 H), 7.48 (d, 2 H), 7.58 (d, J = 8.6 Hz, 2 H),7.80 (s, 4 H); MS m/z 476.1 (M + H)⁺  83

4′-(3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4-oxo-1,3-diazaspiro[4.4]non-1-en-2-yl)biphenyl-3-carbonitrile MS m/z 467.3 (M + H)⁺  84

N-[4′-(3-{(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4-oxo-1,3-diazaspiro[4.4non-1-en-2-yl)biphenyl-3-yl]methanesulfonamide ¹H NMR (400 MHz, CDCl₃) δ ppm0.71- 0.85 (m, 2 H), 0.91-1.06 (m, 2 H), 1.45- 1.81 (m, 2 H), 1.92-2.18(m, 5 H), 2.19- 2.46 (m, 4 H), 2.47-2.78 (m, 1 H), 3.01 (s, 3 H),3.04-4.00 (m, 6 H), 7.16-7.24 (m, 2 H), 7.25-7.31 (m, 1 H), 7.32-7.42(m, 1 H), 7.55-7.65 (m, 2 H), 7.78-7.89 (m, 2 H), 8.06 (br. s., 1 H); MSm/z 535.2 (M + H)⁺  85

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4′-methoxybiphenyl-4-yl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.68-0.83 (m, 2 H), 0.92-1.03 (m, 2 H), 1.38- 1.72 (m, 2 H), 1.84-2.34 (m, 8H), 2.35- 2.63 (m, 1 H), 3.05-3.31 (m, 1 H), 3.31- 3.75 (m, 3 H),3.80-3.96 (m, 4 H), 7.03 (d, J = 8.6 Hz, 2 H), 7.60 (d, J = 8.6 Hz, 2H), 7.78 (s, 4 H); MS m/z 472.2 (M + H)⁺  18

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-pyridin-2-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-oneMS m/z 443.3 (M + H)⁺ INT-E

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-phenyl-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 366.3 (M + H)⁺  33

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-6-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77(dd, J = 7.6, 2.5 Hz, 2 H), 0.91-1.03 (m, 2 H), 1.41-1.72 (m, 2 H),1.88-2.36 (m, 9 H), 2.39-2.63 (m, 1 H), 3.28 (dd, J = 10.1, 7.6 Hz, 1H), 3.32-3.75 (m, 3 H), 3.83- 3.96 (m, 2 H), 6.61 (br. s., 1 H), 7.32(t, J = 2.8 Hz, 1 H), 7.39 (d, J = 9.1 Hz, 1 H), 7.65 (s, 1 H), 7.74 (d,J = 8.6 Hz, 1 H), 7.76- 7.81 (m, 2 H), 7.82-7.88 (m, 2 H), 8.60- 8.70(m, 1 H); MS m/z 481.2 (M + H)⁺  34

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-6-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.72- 0.84 (m, 2 H), 0.94-1.04 (m, 2 H), 1.41- 1.76 (m, 2 H),1.86-2.36 (m, 9 H), 2.38- 2.67 (m, 1 H), 3.06-3.34 (m, 1 H), 3.34- 3.65(m, 2 H), 3.65-3.77 (m, 1 H), 3.80- 4.01 (m, 2 H), 4.18 (s, 3 H), 7.44(d, J = 8.1 Hz, 1 H), 7.64 (s, 1 H), 7.82-7.88 (m, 3 H), 7.89-7.95 (m, 2H), 8.07 (s, 1 H); MS m/z 496.4 (M + H)⁺  35

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.70- 0.83 (m, 2 H), 0.93-1.04 (m, 2 H), 1.40- 1.75 (m, 2 H),1.87-2.36 (m, 9 H), 2.38- 2.67 (m, 1 H), 3.06-3.33 (m, 1 H), 3.33- 3.76(m, 3 H), 3.81-3.98 (m, 2 H), 4.13 (s, 3 H), 7.53 (d, J = 9.1 Hz, 1 H),7.70 (d, J = 9.1 Hz, 1 H), 7.83 (d, 2 H), 7.88 (d, 2 H), 8.01 (s, 1 H),8.10 (s, 1 H); MS m/z 496.4 (M + H)⁺  91

3-{[(3R)-1-(Cycloprropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4′-(2H-tetrazol-5-yl)biphenyl-4-yl]-1,3-diazaspiro[4.4]non-1- en-4-one MS m/z 509.9 (M +H)⁺  92

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indazol-4-yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.65-0.79 (m, 2 H), 0.87-1.03 (m, 2 H), 1.43- 1.73 (m, 2 H), 1.81-2.01 (m, 4H), 2.02- 2.20 (m, 5 H), 2.34-2.59 (m, 1 H), 3.02- 3.30 (m, 1 H),3.30-3.85 (m, 5 H), 7.27- 7.32 (m, 1 H), 7.43-7.52 (m, 1 H), 7.52- 7.59(m, 1 H), 7.69-7.79 (m, 2 H), 7.79- 7.89 (m, 2 H), 8.19 (br. s., 1 H);MS m/z 482.0 (M + H)⁺  94

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(2′,4′-dichloro-3- methylbiphenyl-4-yl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.63- 0.83(m, 2 H), 0.85-1.05 (m, 2 H), 1.38- 1.71 (m, 2 H), 1.74-2.19 (m, 9 H),2.37 (s, 3 H), 2.39-2.52 (m, 1 H), 2.95-3.24 (m, 1 H), 3.25-3.41 (m, 1H), 3.43-3.71 (m, 4 H), 7.27-7.31 (m, 1 H), 7.31-7.43 (m, 4 H), 7.52 (s,1 H); MS m/z 523.8 (M + H)⁺  39

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one 1H NMR (300 MHz, CDCl₃) δppm 0.63- 0.76 (m, 2 H), 0.84-0.96 (m, 2 H), 1.19- 1.37 (m, 2 H),1.73-1.83 (m, 2 H), 1.83- 1.93 (m, 2 H), 2.77-2.94 (m, 1 H), 3.61 (dd, J= 9.8, 5.6 Hz, 1 H), 3.91-4.04 (m, 2 H), 4.04-4.11 (m, 1 H), 4.14 (s, 3H), 4.24 (t, J = 8.2 Hz, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.63-7.74 (m,3 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.99 (s, 1 H), 8.07 (s, 1 H); MS m/z454 (M + H)⁺ m.p. 191.8° C.  38

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one 1H NMR (300 MHz, CDCl₃) δppm 0.64- 0.74 (m, 2 H), 0.87-0.94 (m, 2 H), 1.23- 1.36 (m, 2 H),k1.75-1.84 (m, 2 H), 1.84- 1.93 (m, 2 H), 2.79-2.94 (m, 1 H), 3.61 (dd, J= 9.8, 5.6 Hz, 1 H), 3.90-4.04 (m, 2 H), 4.04-4.14 (m, 1 H), 4.16 (s, 3H), 4.25 (t, J = 8.3 Hz, 1 H), 7.44 (dd, J = 8.5, 1.2 Hz, 1 H), 7.62 (s,1 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.80-7.88 (m, 3 H), 8.04 (s, 1 H); MSm/z 454 (M + H)⁺ m.p. 174.6° C.  51

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.75 (m, 2 H), 0.87-0.97 (m, 2 H), 1.23- 1.37 (m, 1 H), 1.74-1.84 (m, 2H), 1.84- 1.93 (m, 2 H), 2.76-2.96 (m, 1 H), 3.62 (dd, J = 9.8, 5.6 Hz,1 H), 3.90-4.16 (m, 4 H), 4.25 (t, J = 89.3 Hz, 1 H), 7.59 (d, J = 8.7Hz, 1 H), 7.64-7.72 (m, 3 H), 7.79 (d, J = 8.4 Hz, 2 H), 8.02 (s, 1 H),8.16 (s, 1 H), 10.39 (br. s., 1 H); MS m/z 440 (M + H)⁺ m.p. >300° C. 40

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.77(m, 2 H), 0.83-1.01 (m, 2 H), 1.22- 1.37 (m, 1 H), 1.73-1.83 (m, 2 H),1.83- 1.92 (m, 2 H), 2.73-2.97 (m, 1 H), 3.63 (dd, J = 9.9, 5.6 Hz, 1H), 3.88-4.16 (m, 4 H), 4.23 (t, J = 8.2 Hz, 1 H), 6.58-6.69 (m, 1 H),7.29 (d, J = 2.9 Hz, 1 H), 7.44-7.52 (m, 2 H), 7.64 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2 H), 7.92 (s, 1 H), 8.43 (br. s., 1 H); MS m/z439 (M + H)⁺ m.p. 190.8° C.  43

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 404 (M + H)⁺ m.p.164.9° C.  42

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 404 (M + H)⁺ m.p.164.7° C.  41

4′-(6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl-4-carbonitrile 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.76(m, 2 H), 0.85-0.96 (m, 2 H), 1.23- 1.36 (m, 1 H), 1.74-1.83 (m, 2 H),1.83- 1.94 (m, 2 H), 2.70-2.95 (m, 1 H), 3.57 (dd, J = 9.9, 5.6 Hz, 1H), 3.87-4.02 (m, 3 H), 4.02-4.16 (m, 1 H), 4.24 (t, J = 8.3 Hz, 1 H),7.65-7.85 (m, 8 H); MS m/z 425 (M + H)⁺. m.p. 182.8° C.  52

5-[4-(1,3-Benzoxazol-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.65-0.78 (m, 2 H), 0.91 (t, J = 3.7 Hz, 2 H), 1.23- 1.35 (m, 1 H), 1.75-1.84(m, 2 H), 1.88 (quin, J = 3.5 Hz, 2 H), 2.77-2.95 (m, 1 H), 3.62 (dd, J= 9.9, 5.6 Hz, 1 H), 3.88-4.16 (m, 4 H), 4.25 (t, J = 8.2 Hz, 1 H),7.64- 7.75 (m, 4 H), 7.79 (d, J = 8.4 Hz, 2 H), 8.05 (s, 1 H), 8.17 (s,1 H); MS m/z 441 (M + H)⁺  53

5-(3′-Amino-4′-hydroxybiphenyl-4-yl)-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)⁺  54

N-[4′-(6-{[-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-4-hydroxybiphenyl-3- yl]formamide MS m/z 431 (M + H)⁺  50

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.65- 0.80(m, 2 H), 0.89-1.01 (m, 2 H), 1.23- 1.38 (m, 1 H), 1.73-1.84 (m, 2 H),1.84- 1.95 (m, 2 H), 2.75-2.96 (m, 1 H), 3.61 (dd, J = 10.0, 5.7 Hz, 1H), 3.84-4.15 (m, 4 H), 4.27 (t, J = 8.5 Hz, 1 H), 6.82 (d, J = 8.5 Hz,2 H), 7.41 (d, J = 8.5 Hz, 2 H), 7.52- 7.65 (m, 4 H), 7.67 (s, 1 H); MSm/z 416 (M + H)⁺ 120

2-[4-(1-Benzofuran-5-yl)-2-fluorophenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.76 (d, J = 8.1 Hz, 2 H), 0.90-1.07 (m, 2 H), 1.41- 1.73 (m, 2 H),1.81-2.26 (m, 9 H), 2.35- 2.63 (m, 1 H), 2.97-3.28 (m, 1 H), 3.28- 3.79(m, 5 H), 6.87 (s, 1 H), 7.49-7.59 (m, 2 H), 7.63 (d, J = 8.6 Hz, 2 H),7.68-7.80 (m, 2 H), 7.86 (s, 1 H); MS m/z 499.9 (M + H)⁺ 121

2-(4′-Chloro-3-fluorobiphenyl-4-yl)-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.70- 0.89 (m, 2 H), 0.90-1.11 (m, 2 H), 1.39- 1.72 (m, 2 H),1.81-2.28 (m, 9 H), 2.34- 2.62 (m, 1 H), 2.95-3.28 (m, 1 H), 3.29- 3.77(m, 5 H), 7.42-7.52 (m, 3 H), 7.56 (d, J = 8.6 Hz, 3 H), 7.73 (t, J =7.6 Hz, 1 H); MS m/z 493.9 (M + H)⁺ 156

2-[4-(1-Benzofuran-5-yl)-2- methoxyphenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 0.67- 0.84 (m, 2 H), 0.90-1.02 (m, 2 H), 1.38- 1.66 (m, 2 H),1.81-2.64 (m, 10 H), 2.98- 3.22 (m, 1 H), 3.28-3.78 (m, 5 H), 4.00 (s, 3H), 6.86 (d, 1 H), 7.24-7.30 (m, 1 H), 7.40 (d, J = 7.6 Hz, 1 H),7.51-7.58 (m, 1 H), 7.62 (d, 1 H), 7.65-7.76 (m, 2 H), 7.85 (s, 1 H); MSm/z 511.9 (M + H)⁺ 157

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)-2-methoxyphenyl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz,CDCl₃) δ ppm 0.67- 0.82 (m, 2 H), 0.89-1.03 (m, 2 H), 1.38- 1.64 (m, 2H), 1.82-2.63 (m, 10 H), 2.99- 3.20 (m, 1 H), 3.26-3.85 (m, 5 H), 3.93-4.04 (m, 3 H), 6.64 (br. s., 1 H), 7.29 (d, J = 7.1 Hz, 2 H), 7.34-7.44(m, 2 H), 7.44- 7.51 (m, 1 H), 7.61-7.71 (m, 1 H), 7.89 (s, 1 H),8.48-8.64 (m, 1 H); MS m/z 511.0 (M + H)⁺ 178

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-methyl-1-benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CDCl₃) δppm 0.62- 0.73 (m, 2 H), 0.80-0.99 (m, 2 H), 1.24- 1.38 (m, 2 H),1.74-1.82 (m, 2 H), 1.82- 1.93 (m, 2 H), 2.50 (s, 3 H), 2.73-2.94 (m, 1H), 3.62 (dd, J = 9.6, 5.6 Hz, 1 H), 3.85- 4.15 (m, 3 H), 4.23 (t, J =8.2 Hz, 1 H), 6.44 (s, 1 H), 7.40-7.55 (m, 2 H), 7.65 (d, J = 8.1 Hz, 2H), 7.72 (s, 1 H), 7.77 (d, J = 8.2 Hz, 2 H); MS m/z 454 (M + H)⁺ m.p.166.3° C. 179

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.78(m, 2 H), 0.85-1.01 (m, 2 H), 1.27- 1.40 (m, 1 H), 1.70-1.82 (m, 2 H),1.82- 1.95 (m, 2 H), 2.34 (s, 3 H), 2.50 (s, 3 H), 2.75-3.02 (m, 1 H),3.63 (dd, J = 8.6, 5.6 Hz, 1 H), 3.86-4.16 (m, 4 H), 4.25 (t, H = 7.9Hz, 1 H), 6.41 (s, 1 H), 7.15 (d, J = 8.1 Hz, 1 H), 7.44-7.64 (m, 5 H);MS m/z 468 (M + H)⁺ m.p. 170.1° C. 180

5-[4-(1-Benzofuran-5-yl)-3-methylphenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃)δ ppm 0.66- 0.78 (m, 2 H), 0.92-1.02 (m, 2 H), 1.40- 2.11 (m, 7 H), 2.34(s, m3 H), 2.39-2.71 (m, 1 H), 2.96-3.98 (m, 6 H), 6.82 (s, 1 H),7.18-7.31 (m, 1 H), 7.35-7.48 (m, 2 H), 7.49-7.61 (m, 3 H), 7.69 (s, 1H); MS m/z 468 (M + H)⁺ m.p. 71.9° C.

Example 2(R)-5-(4-(Benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(Compound #58)

STEP A: (R)-Cyclopropyl-(3-(hydroxymethyl)pyrrolidin-1-yl)methanone

To a solution of (R)-pyrrolidin-3-ylmethanol (3.45 g, 25.07 mmol) andDIPEA (8.50 mL, 50 mmol) in DCM (100 mL) was added at 0° C.cyclopropanecarbonyl chloride (2.27 mL, 25.1 mmol). After stirring for 5h at room temperature, the reaction mixture was partitioned between DCMand aqueous 1.0M NaOH (100 mL) and water (50 mL). The organic phase waswashed with brine, dried over MgSO₄, filtered and concentrated in vacuoto yield a residue. The residue was purified by flash chromatography(silica gel, 0 to 10% MeOH/DCM) to yield(R)-cyclopropyl(3-(hydroxymethyl)pyrrolidin-1-yl)methanone (2.53 g,60%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.84 (m, 2H), 0.89-1.09 (m, 2H),1.42-2.69 (m, 5H), 3.24 (dd, J=12.1, 7.1 Hz, 0.5H), 3.34-3.52 (m, 1H),3.52-3.89 (m, 4.5H); MS n/z 170 (M+H)⁺.

STEP B: (R)-(1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methylmethanesulfonate

To a solution of(R)-cyclopropyl(3-(hydroxymethyl)pyrrolidin-1-yl)methanone (2.53 g,14.95 mmol) and triethylamine (4.17 mL, 29.9 mmol) in DCM (70 mL) wasadded at 0° C. methanesulfonyl chloride (1.39 mL, 17.9 mmol). Afterstirring overnight at room temperature, the reaction mixture waspartitioned between DCM (100 mL) and water (50 mL). The organic phasewas washed with brine, dried over MgSO₄, filtered and concentrated invacuo to yield a residue. The residue was purified by flashchromatography (silica gel, 0 to 10% MeOH/DCM) to yield(R)-(1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl methanesulfonate(3.41 g, 92%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.88 (m, 2H), 0.87-1.11 (m, 2H),1.50-2.31 (m, 3H), 2.53-2.88 (m, 1H), 3.03 (s, 1.5H), 3.05 (s, 1.5H),3.20-3.37 (m, 0.5H), 3.38-3.56 (m, 1H), 3.57-3.96 (m, 2.5H), 4.05-4.39(m, 2H); MS m/z 248 (M+H)⁺.

STEP C:((R)-5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a stirring solution of5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (1.53 g, 5.77 mmol)and (R)-(1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methylmethanesulfonate (1.43 g, 5.77 mmol) in DMF (25 mL) was added Cs₂CO₃(3.76 g, 11.5 mmol). After stirring at room temperature for 6 h at 65°C., the reaction mixture was filtered through a pad of diatomaceousearth and further washed with EtOAc (3×20 ml). The filtrate wasconcentrated and the residue was partitioned between EtOAc and water.The organic phase was washed with brine, dried over Na₂SO₄, filtered andconcentrated in vacuo to yield a residue. The residue was purified byflash chromatography (silica gel, 100% EtOAc and then 0-10% MeOH/DCM) toyield (R)-5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (1 g, 40%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.82 (m, 2H), 0.86-1.05 (m, 2H),1.38-2.07 (m, 7H), 2.27-2.57 (m, 1H), 2.93-3.08 (m, 0.5H), 3.16-3.39 (m,1H), 3.44-3.84 (m, 4.5H), 7.41-7.54 (m, 2H), 7.62-7.73 (m, 2H); MS m/z416 (M+H)⁺.

STEP D:(R)-5-(4-(Benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a solution of(R)-5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(104 mg, 0.25 mmol) in acetonitrile (2 mL) was added2-(benzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (73.23 mg,0.3 mmol), aqueous 1.0M Na₂CO₃ (0.5 mL, 0.5 mmol) andBis(triphenylphosphine)palladium(II) chloride (9.12 mg, 0.013 mmol). Thereaction mixture was bubbled with nitrogen for 5 min and heated to 85°C. for 2 h under nitrogen atmosphere. The resulting mixture was dilutedwith DCM and the organic layer was filtered and concentrated to yield aresidue which was purified by flash chromatography (silica gel, 0-10%MeOH/DCM) and re-purified by reverse phase prep-HPLC to yield(R)-5-(4-(benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(20 mg, 17%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.79 (m, 2H), 0.88-1.01 (m, 2H),1.39-2.08 (m, 8H), 2.33-2.68 (m, 1H), 2.97-3.17 (m, 0.5H), 3.18-3.43 (m,1H), 3.45-3.94 (m, 4.5H), 6.85 (d, J=1.8 Hz, 1H), 7.51-7.64 (m, 2H),7.64-7.73 (m, 3H), 7.73-7.81 (m, 2H), 7.85 (s, 1H); MS m/z 454.0 (M+H)⁺.

Following the procedure described in Example 2, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  10

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.59-0.82 (m, 2 H), 0.87-0.97 (m, 2 H), 0.97-1.17 (m, 2 H), 1.52-1.92 (m, 9H), 2.34-2.65 (m, 1 H), 2.82-3.11 (m, 1 H), 3.60-3.76 (m, 1 H), 4.15 (d,J = 12.1 Hz, 1 H), 4.53 (d, J = 11.4 Hz, 1 H), 6.63 (t, J = 2.3 Hz, 1H), 7.26 (d, J = 2.9 Hz, 1 H), 7.41-7.55 (m, 2 H), 7.64 (d, J = 8.4 Hz,2 H), 7.79 (d, J = 8.4 Hz, 2 H), 7.93 (s, 1 H), 8.63 (br. s., 1 H); MSm/z 467 (M + H)⁺ m.p. 129.4° C.  9

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1-methyl-1H-pyrazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 432 (M + H)⁺ m.p.144.5° C.  8

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1-methyl-1H-pyrazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z (M + H)⁺ m.p.75.9° C.  7

4′-(6-{[1-(Cyclopropylcarbonyl)piperidin- 4-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 4-carbonitrile MS m/z 453 (M +H)⁺ m.p. 154.5° C.  6

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4-pyridin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 429 (M + H)⁺ m.p. 132.0° C.  20

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4-isoquinolin-6-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.65-0.76 (m, 2 H), 0.88-0.95 (m, 2 H), 0.95-1.23 (m, 2 H), 1.48-1.75 (m, 4H), 1.75-1.83 (m, 2 H), 1.83-1.99 (m, 3 H), 2.48 (t, J = 11.5 Hz, 1 H),2.99 (t, J = 12.1 Hz, 1 H), 3.69 (dd, J = 14.2, 6.9 Hz, 2 H), 4.16 (d, J= 11.8 Hz, 1 H), 4.53 (d, J = 12.1 Hz, 1 H), 7.68-7.79 (m, 3 H), 7.87(d, J = 8.4 Hz, 2 H), 7.91 (dd, J = 8.6, 1.7 Hz, 1 H), 8.04-8.16 (m, 2H), 8.60 (d, J = 5.8 Hz, 1 H), 9.32 (s, 1 H); MS m/z 479 (M + H)⁺ m.p.97.9° C.  19

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)⁺ m.p.107.7° C.  24

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1-methyl-1H-indazol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)⁺ m.p.104.0° C.  29

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.77 (m, 2 H), 0.89-0.97 (m, 2 H), 1.06 (d, J = 19.0 hz, 2 H), 1.51-1.73(m, 3 H), 1.75-1.94 (m, 6 H), 2.49 (t, J = 11.3 Hz, 1 H), 2.99 (t, J =11.8 Hz, 1 H), 3.55-3.82 (m, 2 H), 4.16 (d, J = 12.5 Hz, 1 H), 4.54 (d,J = 11.7 Hz, 1 H), 7.58 (m, J = 8.7 Hz, 1 H), 7.63-7.73 (m, 3 H), 7.77(m, J = 8.2 Hz, 2 H), 8.02 (s, 1 H), 8.16 (br. s., 1 H); MS m/z 468 (M +H)⁺ m.p. 179.9° C.  25

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4-isoquinolin-7-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 479 (M + H)⁺ m.p. 151.1° C. 30

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4-isoquinolin-7-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.60-0.78 (m, 2 H), 0.87-1.03 (m, 2 H), 1.42-2.08 (m, 7.5 H), 2.33-2.50 (m,0.5 H), 2.51-2.68 (m, 0.5 H), 3.05 (dd, J = 12.0, 7.2 Hz, 0.5 H),3.17-3.44 (m, 1 H), 3.49-3.89 (m, 4 H), 7.66-7.80 (m, 3 H), 7.83-7.92(m, 2 H), 7.92-8.05 (m, 2 H), 8.23 (s, 1 H), 8.59 (br. s., 1 H), 9.37(br. s., 1 H); MS m/z 465 (M + H)⁺ m.p. 92.3° C.  28

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.61- 0.79 (m, 2 H), 0.84-1.05 (m, 2 H), 1.38-2.09 (m, 8 H),2.37-2.51 (m, 0.5 H), 2.52-2.67 (m, 0.5 H), 3.06 (dd, J = 12.0, 7.1 Hz,0.5 H), 3.22-3.39 (m, 1 H), 3.47-3.92 (m, 4.5 H), 4.13 (s, 3 H), 7.50(d, J = 8.7 Hz, 1 H), 7.63-7.73 (m, 3 H), 77.3-7.83 (m, 2 H), 7.98 (s, 1H), 8.06 (s, 1 H); MS m/z 468 (M + H)⁺ m.p. 169.6° C.  27

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.57- 0.81 (m, 2 H), 0.83-1.05 (m, 2 H), 1.38-2.12 (m, 8 H),2.34-2.50 (m, 0.5 H), 2.51-2.69 (m, 0.5 H), 2.97-3.14 (m, 0.5 H),3.18-3.43 (m, 1 H), 3.43- 3.97 (m, 4.5 H), 4.15 (s, 3 H), 7.43 (d, J =8.0 Hz, 1 H), 7.61 (br. s., 1 H), 7.65- 7.77 (m, 2 H), 7.77-7.93 (m, 3H), 8.03 (br. s., 1 H); MS m/z 468 (M + H)⁺ m.p. 138.2° C.  31

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.83 (m, 2 H), 0.83-1.07 (m, 2 H), 1.39-2.09 (m, 8 H), 2.32-2.65 (m, 1H), 3.09 (dd, J = 12.0, 6.8 Hz, 0.5 H), 3.19-3.41 (m, 1 H), 3.42-3.97(m, 4.5 H), 6.62 (br. s., 1 H), 7.27 (s, 1 H), 7.46 (d, J = 3.0 Hz, 2H), 7.65 (dd, J = 8.0, 4.2 Hz, 2 H), 77.3-7.84 (m, 2 H), 7.91 (s, 1 H),8.65 (br. s., 1 H); MS m/z 453 (M + H)⁺ m.p. 178.2° C.  47

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4-isoquinolin-6-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.78 (m, 2 H), 0.87-1.01 (m, 2 H), 1.41-1.58 (m, 1.5 H), 1.65-2.10 (m,5.5 H), 2.35-2.69 (m, 1 H), 3.05 (dd, J = 12.0 Hz, 7.2 Hz, 1 H),3.23-3.41 (m, 0.5 H), 3.49-3.89 (m, 4.5 H), 7.70-7.80 (m, 3 H),7.84-7.94 (m, 3 H), 8.07 (s, 1 H), 8.11 (d, J = 8.5 Hz, 1 H), 8.60 (d, J= 5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 465 (M + H)⁺ m.p. 162.3° C.  64

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.68-0.83 (m, 2 H), 0.92-1.07 (m, 2 H), 1.38-2.16 (m, 7 H), 2.34-2.72 (m, 1H), 3.05 (dd, J = 12.0, 7.2 Hz, 0.5 H), 3.17-3.99 (m, 5.5 H), 6.72-6.93(m, 23 H), 7.32-7.50 (m, 2 H), 7.54-7.74 (m, 4 H), 7.80-8.25 (m, 1 H);MS m/z 430 (M + H)⁺  48

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 4-carbonitrile ¹H NMR (300 MHz,CDCl₃) δ ppm 0.66- 0.77 (m, 2 H), 0.89-1.00 (m, m2 H), 1.42-1.56 (m, 1.5H), 1.64-2.11 (m, 5.5 H), 2.31-2.67 (m, 1 H), 3.02 (dd, J = 12.1, 7.3Hz, 0.5 H), 3.22-3.39 (m, ,1 H), 3.44-3.92 (m, 4.5 H), 7.67-7.89 (m, 8H); MS m/z 439 (M + H)⁺ m.p. 90.7° C.  32

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4-pyridin-4-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 429 (M + H)⁺ m.p. >300° C.  26

5-[4-(1H-Benzimidazol-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.56- 1.40 (m, 8 H), 1.45-2.01 (m, 6 H), 2.39-2.62 (m, 1 H),2.84-3.13 (m, 1 H), 3.55-3.82 (m, 3 H), 4.05-4.27 (m, 1 H), 4.41-4.62(m, 1 H), 7.42-7.94 (m, 8 H), 8.13 (br. s., 1 H); MS m/z 468 (M + H)⁺m.p. 144° C.  37

5-[4-(1,3-Benzoxazol-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 469 (M + H)⁺  55

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. 161.7° C. 57

5-[4-(1,3-Benzothiazol-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.41- 0.73 (m, 2 H), 0.79-0.89 (m, 1 H), 1.39-1.90 (m, 9 H),2.23-2.53 (m, 1 H), 2.76-3.06 (m, 1 H), 3.22-3.49 (m, 2 H), 3.49-3.80(m, 3 H), 3.93-4.24 (m, 1 H), 4.24-4.60 (m, 1 H), 7.53- 7.85 (m, 5 H),8.00 (d, J = 8.0 Hz, 1 H), 8.34 (br. s., 1 H), 9.00 (br. s., 1 H); MSm/z 485 (M + H)⁺ m.p. 152.6° C.  71

5-[4-(1,3-Benzothiazol-5-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz,DMSO-d6) δ ppm 0.47-0.76 (m, 4 H), 1.29-1.67 (m, 4.5 H), 1.67-1.82 (m, 2H), 1.82-1.97 (m, 1 H), 2.18-2.45 (m, 1 H), 2.90 (dd, J = 11.5, 6.8 Hz,0.5 H), 3.05-3.28 (m, 2 H), 3.40-3.63 (m, 2 H), 3.68-3.85 (m, 2 H),7.78-7.86 (m, 1 H), 7.90 (d, J = 8.2 Hz, 1 H), 7.99 (d, J = 7.1 Hz, 2H), 8.30 (d, J = 8.2 Hz, 1 H), 8.46 (br. s., 1 H), 9.47 (s, 1 H) MS m/z471 (M + H)⁺ m.p. 82.7° C. 105

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-fluorobiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.75(m, 2 H), 0.90-0.98 (m, 2 H), 1.41-1.59 (m, 2 H), 1.65-2.08 (m, 5 H),2.31-2.67 (m, 1 H), 3.04 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.21-3.38 (m, 1H), 3.50-3.90 (m, 4.5 H), 7.18 (t, J = 8.7 Hz, 2 H), 7.56-7.64 (m, 2 H),7.64- 7.75 (m, 4 H); MS m/z 432 (M + H)⁺ m.p. 153.7° C. 104

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′-(trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 482 (M + H)⁺ m.p. 253.8° C. 115

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(3′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61-0.88 (m, 2 H), 0.89-1.13 (m, 2 H), 1.39-2.18 (m, 7 H), 2.34-2.71 (m, 1H), 2.92-4.20 (m, 6 H), 6.64-6.98 (m, 2 H), 6.97-7.18 (m, 1 H),7.18-7.41 (m, 1 H), 7.45-7.87 (m, 4 H), 8.07- 8.57 (m, 1 H); MS m/z 430(M + H)⁺ m.p. >300° C. 103

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-methoxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.75 (m, 2 H), 0.88-0.98 (m, 2 H), 1.41-1.57 (m, 2 H), 1.62-2.01 (m, 6H), 2.32-2.63 (m, 0.5 H), 3.18-3.37 (m, 1 H), 3.49-3.86 (m, 4.5 H), 3.87(s, 3 H), 7.01 (d, J = 8.7 Hz, 2 H), 7.57 (d, J = 8.7 Hz, 2 H), 7.64(dd, J = 8.4, 1.9 Hz, 2 H), 7.69 (dd, J = 8.4, 3.8 Hz, 2 H); MS m/z 444(M + H)⁺ m.p. 76.6° C. 102

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(3′-fluorobiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.78(m, 2 H), 0.86-1.02 (m, 2 H), 1.41-2.08 (m, 7 H), 2.33-2.65 (m, 1 H),3.04 (dd, J = 12.1, 7.1 Hz, 0.5 H), 3.20-3.39 (m, 1 H), 3.50-3.90 (m,4.5 H), 7.05-7.16 (m, 1 H), 7.30-7.38 (m, 1 H), 7.38-7.51 (m, 2 H),7.65-7.78 (m, 4 H); MS m/z 432 (M + H)⁺ m.p. 131.1° C. 101

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(3′-methylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71(dd, J = 7.7, 3.0 Hz, 2 H), 0.87-1.02 (m, 2 H), 1.42-2.08 (m, 7 H),2.35-2.62 (m, 1 H), 2.45 (s, 3 H), 3.06 (dd, J = 12.0, 7.0 Hz, 0.5 H),3.20-3.39 (m, 1 H), 3.43-3.90 (m, 4.55 H), 7.23 (d, J = 7.0 Hz, 1 H),7.33-7.51 (m, 3 H), 7.63-7.70 (m, 2 H), 7.70-7.79 (m, 2 H); MS m/z 428(M + H)⁺ m.p. >300° C. 100

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-methylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.78 (m, 2 H), 0.90-1.00 (m, 2 H), 1.38-2.10 (m, 7 H), 2.35-2.69 (m, 1H), 2.41-2.44 (m, 3 H), 3.06 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.14-3.41(m, 1 H), 3.40-3.93 (m, 4.5 H), 7.29 (d, J = 8.1 Hz, 2 H), 7.54 (d, J =8.1 Hz, 2 H), 7.61-7.69 (m, 2 H), 7.69-7.78 (m, 2 H); MS m/z 428 (M +H)⁺ m.p. 123.3° C. 114

5-(4′-Chlorobiphenyl-4-yl)-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.62- 0.81 (m, 2 H), 0.86-1.04 (m, 2 H), 1.38-2.10 (m, 7 H),2.30-2.66 (m, 1 H), 3.04 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.18-3.41 (m, 1H), 3.42-3.93 (m, 4.5 H), 7.45 (d, J = 8.1 Hz, 2 H), 7.57 (d, J = 8.5Hz, 2 H), 7.63-7.80 (m, 4 H); MS m/z 448 (M + H)⁺ 113

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(3′-methoxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.60-0.81 (m, 2 H), 0.83-1.04 (m, 2 H), 1.37-2.10 (m, 7 H), 2.26-2.67 (m, 1H), 2.91-3.87 (m, 6 H), 3.89 (s, 3 H), 6.95 (d, J = 8.0 Hz, 1 H),7.11-7.26 (m, 2 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.56-7.86 (m, 4 H); MSm/z 444 (M + H)⁺ 112

5-(3′-Chlorobiphenyl-4-yl)-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.63- 0.78 (m, 2 H), 0.86-1.04 (m, 2 H), 1.38-2.09 (m, 7 H),2.31-2.66 (m, 1 H), 3.04 (dd, J = 12.0, 7.0 Hz, 0.5 H), 3.17-3.40 (m, 1H), 3.50-3.91 (m, 4.5 H), 7.34-7.47 (m, 2 H), 7.47-7.56 (m, 1 H), 7.62(s, 1 H), 7.65-7.78 (m, 4 H); MS m/z 448 (M + H)⁺ m.p. 129.4° C. 123

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 3-carbonitrile MS m/z 439 (M +H)⁺ m.p. 171.4° C. 145

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(dimethylamino)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, DMSO-d6) δ ppm 0.56-0.70 (m, 4 H), 1.31-1.67 (m, 4 H),1.67-1.94 (m, 3 H), 2.16-2.45 (m, 1 H), 2.89 (dd, J = 11.8, 6.9 Hz, 0.5H), 2.97 (s, 6 H), 3.06-3.30 (m, 1.5 H), 3.37-3.65 (m, 2 H), 3.74 (t, J= 7.1 Hz, 2 H), 6.78 (dd, J = 8.1, 1.8 Hz, 1 H), 6.95- 7.04 (m, 2 H),7.30 (m, J = 8.1, 8.1 Hz, 1 H), 7.71-7.79 (m, 2 H), 7.79-7.88 (m, 2 H);MS m/z 457 (M + H)⁺ m.p. 74.0° C. 124

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′-(dimethylamino)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.2 Hz, 4 H), 1.47-1.66 (m, 4 H),1.67-1.94 (m, 3 H), 2.16-2.44 (m, 1 H), 2.89 (dd, J = 11.8, 6.9 Hz, 0.5H), 2.96 (s, 6 H), 3.06-3.30 (m, 2 H), 3.36-3.60 (m, 1.5 H), 3.74 (t, J= 76.7 Hz, 2 H), 6.82 (d, J = 8.7 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H),7.66-7.80 (m, 4 H); MS m/z 457 (M + H)⁺ m.p. 274.9° C. 125

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′-(trifluoromethoxy)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)⁺ m.p. 146.2° C. 126

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, CDCl₃) δ ppm 0.62- 0.80 (m, 2 H), 0.88-1.04 (m, 2 H),1.39-1.60 (m, 2 H), 1.73-2.12 (m, 5 H), 2.31-2.67 (m, 1 H), 3.04 (dd, J= 11.8, 7.1 Hz, 0.5 H), 3.19-3.40 (m, 1 H), 3.40-3.94 (m, 4.5 H),7.55-7.95 (m, 8 H); MS m/z 482 (M + H)⁺ m.p. 120.5° C. 146

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(trifluoromethoxy)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)⁺ m.p. 76.3° C. 111

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(3′-methylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 442 (M + H)⁺ m.p. 101.9° C. 97

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-methylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 442 (M + H)⁺ m.p. 167.1° C. 99

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-methylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 458 (M + H)⁺ m.p. >300° C.  98

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(2′-methoxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 458 (M + H)⁺ m.p. >300° C. 110

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-fluorobiphenyl-4-yl)- diazaspiro[2.4]hept-4-en-7-one MSm/z 446 (M + H)⁺ m.p. 169.9° C. 109

5-(4′-Chlorobiphenyl-4-yl)-6-{[1- (cyclopropylcarbonyl)piperidin-4-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 462 (M + H)⁺ m.p.196.8° C.  55

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. 153.1° C.108

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(3′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. >300° C. 107

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4′-(trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 496 (M + H)⁺ m.p. 187.7° C. 158

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(3′-fluorobiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 446 (M + H)⁺

Example 3(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one(Compound #65)

STEP A:(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one(Compound #64)

(R)-5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(0.465 g, 1.117 mmol), (4-hydroxyphenyl)boronic acid (0.2 g, 1.45 mmol),tetrakis(triphenylphosphine) palladium (0.063 g, 0.055 mmol), aqueous1.0M sodium carbonate (2.23 mL, 2.23 mmol) and 1,4-dioxane (5 mL) werecombined and bubbled with nitrogen for 5 min. The resulting mixture washeated to reflux under nitrogen for 3 h. The resulting mixture wasdiluted with DCM (30 mL), dried over MgSO₄, filtered and concentrated invacuo to yield a residue which was purified by flash chromatography(silica gel 0-10% MeOH in DCM) to yield(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one(175 mg, 36%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.68-0.83 (m, 2H), 0.92-1.07 (m, 2H),1.38-2.16 (m, 7H), 2.34-2.72 (m, 1H), 3.05 (dd, J=12.0, 7.2 Hz, 0.5H),3.17-3.99 (m, 5.5H), 6.72-6.93 (m, 2H), 7.32-7.50 (m, 2H), 7.54-7.74 (m,4H), 7.80-8.25 (m, 1H); MS m/z 430.0 (M+H)⁺.

STEP B:(R)-4′-(6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl]-4-yltrifluoromethanesulfonate

To a solution of(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one(175 mg, 0.407 mmol) in DCM (5 mL) and pyridine (1 mL) was added at 0°C. trifluoromethanesulfonic anhydride (0.082 mL, 0.488 mmol). Afterstirring for 2 h at room temperature, the reaction mixture was quenchedwith water and partitioned between 1.0M aqueous solution of Na₂CO₃ andDCM. The organic phase was dried over MgSO₄, filtered and concentratedin vacuo to yield residue which was purified by flash chromatography(silica gel, 0 to 5% MeOH in DCM) to yield(R)-4′-(6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)[1,1′-biphenyl]-4-yltrifluoromethanesulfonate (81 mg, 35%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.78 (m, 2H), 0.88-0.99 (m, 2H),1.39-1.58 (m, 2H), 1.63-1.93 (m, 5H), 1.95-2.06 (m, 1H), 2.31-2.67 (m,1H), 3.02 (dd, J=12.0, 7.2 Hz, 0.5H), 3.21-3.40 (m, 1H), 3.47-3.86 (m,4.5H), 7.40 (d, J=8.7 Hz, 2H), 7.64-7.76 (m, 6H); MS m/z 562.0 (M+H)⁺.

STEP C:(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)ethyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a solution of(R)-4′-(6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl]-4-yltrifluoromethanesulfonate (75 mg, 0.134 mmol) in acetonitrile (2 mL) wasadded1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(33.5 mg, 0.161 mmol), aqueous 1.0M Na₂CO₃ (0.27 mL, 0.27 mmol) andbis(triphenylphosphine) palladium (II) chloride (4.91 mg, 0.007 mmol).The resulting mixture was bubbled with nitrogen for 5 min and heated to85° C. for 2 h. The resulting mixture was diluted with DCM (30 mL),dried over MgSO₄, filtered and concentrated in vacuo to yield a residuewhich was purified by flash chromatography (silica gel, 0 to 5% MeOH inDCM) to yield a residue which was re-crystallized from MeCN to yield(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one(41 mg, 60%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.77 (m, 2H), 0.90-1.00 (m, 2H),1.42-1.73 (m, 2H), 1.73-1.84 (m, 2H), 1.84-1.92 (m, 2H), 1.92-2.10 (m,1H), 2.36-2.66 (m, 1H), 3.06 (dd, J=12.0, 7.1 Hz, 0.5H), 3.20-3.40 (m,1H), 3.50-3.89 (m, 4.5H), 3.98 (s, 3H), 7.59 (m, J=8.2 Hz, 2H),7.62-7.72 (m, 5H), 7.73-7.80 (m, 2H), 7.83 (s, 1H); MS m/z 494.0 (M+H)⁺.

Following the procedure described in Example 3, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  21

5-(4″-Bromo-1,1′:4′,1″-terphenyl-4-yl)-6-{[1-(cyclopropylcarbonyl)piperidin-4-yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, CDCl₃) δppm 0.66- 0.76 (m, 2 H), 0.87-0.96 (m, 2 H), 0.96-1.21 (m, 2 H),1.49-1.56 (m, 1 H), 1.61-1.73 (m, 2 H), 1.73-1.83 (m, 2 H), 1.83-1.93(m, 3 H), 2.48 (t, J = 12.2 Hz, 1 H), 2.99 (t, J = 11.8 Hz, 1 H), 3.69(t, J = 8.2 Hz, 2 H),k 4.16 (d, J = 11.8 Hz, 1 H), 4.53 (d, J = 10.9 Hz,1 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.61 (d, J = 8.5 Hz, 2 H), 7.65-7.85(m, 8 H); MS m/z 582 (M + H)⁺ m.p. 241.1° C.  23

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm0.71 (dd, J = 7.8, 3.1 Hz, 2 H), 0.89-0.97 (m, 2 H), 0.97-1.11 (m, 2 H),1.47- 1.73 (m, 3 H), 1.73-1.83 (m, 2 H), 1.83-1.96 (m, 3 H), 2.49 (t, J= 12.3 Hz, 1 H), 2.99 (t, J = 12.8 Hz, 1 H), 3.69 (t, J = 8.1 Hz, 2 H),4.03-4.32 (m, 1 H), 4.53 (d, J = 10.3 Hz, 1 H), 7.42 (dd, J = 7.6, 4.9Hz, 1 H), 7.71 (t, J = 8.7 Hz, 4 H), 7.79 (dd, J = 8.3, 2.3 Hz, 4 H),7.95 (d, J = 8.0 Hz, 1 H), 8.64 (d, J = 3.6 Hz, 1 H), 8.93 (br. s., 1H); MS m/z 505 (M + H)⁺ m.p. 155.1° C.  56

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4′-(1-methyl-1H-p;yrazol- 4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (dd, J= 7.8, 3.1 Hz, 2 H), 0.88-0.96 (m, 2 H), 0.97-1.33 (m, 3 H), 1.67 (td, J= 8.2, 4.3 Hz, 2 H), 1.73-1.81 (m, 2 H), 1.82-1.94 (m, 3 H), 2.33-2.63(m, 1 H), 2.85-3.09 (m, 1 H), 3.60-3.75 (m, 2 H), 3.98 (s, 3 H),4.06-4.27 (m, 1 H), 4.40-4.65 (m, 1 H), 7.55-7.62 (m, 2 H), 7.62-7.72(m, 5 H), 7.72- 7.80 (m, 2 H), 7.83 (s, 1 H); MS m/z 508 (M + H)⁺ m.p.186.8° C.  61

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-(4′-pyridin-4-ylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 505 (M + H)⁺ m.p. 162.1°C.  62

6-{[1-(Cyclopropylcarbonyl)piperidin-4-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol- 5-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)⁺ m.p. 119.2° C. 122

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm0.61-0.83 (m, 2 H), 0.84-1.06 (m, 2 H), 1.36-2.13 (m, 6 H), 2.28-2.71(m, 1 H), 3.06 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.21-3.41 (m, 1 H),3.41-4.03 (m, 4.5 H), 7.43 (d, J = 4.7 Hz, 1 H), 7.60- 7.89 (m, 8 H),7.95 (d, J = 7.7 Hz, 1 H), 8.64 (br. s., 1 H), 8.93 (br. s., 1 H); MSm/z 491 (M + H)⁺ m.p. 149.7° C.  59

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol- 4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.84(m, 2 H), 0.84-1.06 (m, 2 H), 1.23-1.38 (m, 1 H), 1.72-1.84 (m, 2 H),1.84-1.99 (m, 2 H), 2.75-3.00 (m, 1 H), 3.61 (dd, J = 9.8, 5.6 Hz, 1 H),3.90-4.15 (m, 4 H), 4.00 (s, 3 H), 4.23 (t, J = 8.2 Hz, 1 H), 7.54-7.72(m, 6 H), 7.72-7.96 (m, 4 H); MS m/z 480 (M + H)⁺ m.p. 203.4° C.  60

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm0.65- 0.77 (m, 2 H), 0.91 (t, J = 3.9 Hz, 2 H), 1.25-1.36 (m, 1 H),1.75-1.84 (m, 2 H), 1.84-1.94 (m, 2 H), 2.77-2.96 (m, 1 H), 3.61 (dd, J= 9.9, 5.8 Hz, 1 H), 3.89-4.16 (m, 4 H), 4.25 (t, J = 8.3 Hz, 1 H), 7.42(dd, J = 7.9, 4.9 Hz, 1 H), 7.66-7.89 (m, 8 H), 7.95 (dt, J = 7.9, 1.9Hz, 1 H), 8.64 (dd, J = 4.8, 1.5 Hz, 1 H), 8.93 (d, J = 2.2 Hz, 1 H); MSm/z 477 (M + H)⁺

Example 42-[4-(1,3-Benzoxazol-2-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one(Compound #36)

To a flask under argon was added(R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(122 mg, 0.275 mmol), benzo[d]oxazole (40 mg, 0.329 mmol), K₂CO₃ (76 mg,0.549 mmol), Pd(OAc)₂ (1.3 mg, 0.0055 mmol), Cu(OAc)₂ (10.7 mg, 0.0549mmol), PPh₃ (36 mg, 0.137 mmol) and 1 mL of toluene. The reactionmixture was heated at 110° C. for 6 hrs, the solvent evaporated, and theresidue purified by preparative reverse-phase chromatography to yield2-[4-(1,3-benzoxazol-2-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one(65.3 mg, 47%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.79 (d, J=5.1 Hz, 2H), 0.92-1.07 (m, 2H),1.40-1.76 (m, 2H), 1.83-2.31 (m, 9H), 2.33-2.58 (m, 1H), 3.03-3.32 (m,1H), 3.32-3.91 (m, 5H), 7.39-7.49 (m, 2H), 7.65 (d, J=6.6 Hz, 1H), 7.86(t, J=7.3 Hz, 3H), 8.49 (d, J=6.6 Hz, 2H). MS m/z 483.3 (M+H)⁺.

Example 5 (R)-Methyl2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(Compound #14)

STEP A: 4-tert-Butyl4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate

A mixture tert-butyl 4-amino-4-carbamoylpiperidine-1-carboxylate (0.848g, 3.41 mmol), 4-bromobenzoic acid (0.687 g, 3.41 mmol), EDCI (0.655 g,3.41 mmol), HOBt (0.462 g, 3.41 mmol) and DIPEA (0.59 mL, 3.41 mmol) inDMF (16 mL) was stirred at room temperature for 1 day. The reactionmixture was partitioned between EtOAc and aqueous saturated NaHCO₃. Theorganic phase was washed with brine, dried over Na₂SO₄, filtered andconcentrated in vacuo to yield 4-tert-butyl4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate (1.21 g, 83%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.40 (s, 9H), 1.76-1.93 (m, 2H),2.01-2.19 (m, 2H), 3.09 (br. s., 2H), 3.57-3.80 (m, 2H), 6.93 (br. s.,1H), 7.16 (br. s., 1H), 7.68 (d, J=8.6 Hz, 2H), 7.84 (d, J=8.6 Hz, 2H),8.21 (s, 1H); MS m/z 450.1 (M+Na)⁺).

STEP B: tert-Butyl2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

A mixture of 4-tert-butyl4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate (1.6 g, 3.75mmol) and NaOH (0.75 g, 18.76 mmol) in H₂O (3.80 mL) and MeOH (65 mL)was stirred at 65° C. for 1 day. The reaction mixture was partitionedbetween water (400 mL) and EtOAc (2×350 mL). The organic phase waswashed with brine, dried over Na₂SO₄, filtered and concentrated in vacuoto yield 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (1.53 g,100%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.35-1.53 (m, 11H), 1.61-1.74 (m, 2H),3.28 (br. s., 3H), 3.80-3.98 (m, 2H), 7.77 (d, J=8.3 Hz, 2H), 7.94 (d,J=8.1 Hz, 2H); MS m/z 410.0 (M+H)⁺.

STEP C: 2-(4-Bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (tert-butyl2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(400 mg, 0.98 mmol) in 1,4-dioxane (7 mL) was added 4M HCl in1,4-dioxane (8 mL). After stirring at room temperature for 5 h, thereaction mixture was concentrated to yield2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one as itscorresponding HCl salt, as a solid; which was directly used in the nextstep.

MS m/z 310.0 (M+H)⁺.

STEP D: Methyl2-(4-bromophenyl-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one HCl salt (172 mg,0.5 mmol) in DCM (15 mL) and DIPEA (0.43 mL, 2.5 mmol) was added methylchloroformate (49.6 mg, 0.52 mmol) at 0° C. After stirring at roomtemperature overnight, the reaction mixture was partitioned betweenaqueous NaHCO₃ and DCM. The organic phase was washed with brine, driedover Na₂SO₄, filtered and concentrated in vacuo to yield methyl2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(183 mg, 100%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.52-1.64 (m, 2H), 1.89-2.07 (m, 2H),3.45-3.59 (m, 2H), 3.76 (s, 3H), 3.98-4.25 (m, 2H), 7.64-7.71 (m, 2H),7.77-7.84 (m, 2H); MS n/z 368.0 (M+H)⁺.

STEP E: (S)-Methyl2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of methyl2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(100 mg, 0.27 mmol) and (R)-tert-butyl3-(bromomethyl)pyrrolidine-1-carboxylate (144 mg, 0.54 mmol) in DMF (4.5mL) was added Cs₂CO₃ (222 mg, 0.68 mmol). After stirring at roomtemperature for 5 min and 65° C. for 17 h, the reaction mixture waspartitioned between aqueous NaHCO₃ and EtOAc. The organic phase waswashed with brine, dried over Na₂SO₄, filtered and concentrated in vacuoto yield a residue. The residue was purified by flash chromatography(silica gel, 40% EtOAc/heptane) to yield (S)-methyl2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(122 mg, 81%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.17 (br. s., 1H), 1.41 (s, 9H), 1.46-1.56(m, 2H), 1.67-1.82 (m, 2H), 1.87-2.02 (m, 2H), 2.23 (d, J=6.8 Hz, 1H),2.71-2.87 (m, 1H), 3.09-3.39 (m, 2H), 3.47 (s, 3H), 3.53-3.68 (m, 2H),3.72 (s, 3H), 3.94-4.20 (m, 2H), 7.45 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.1Hz, 2H); MS n/z 540.0 (M+H)⁺.

STEP F: (R)-Methyl2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of (S)-methyl2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(162 mg, 0.295 mmol) in 1,4-dioxane (3 mL) was added 4M HCl in1,4-dioxane (5 mL). After stirring overnight at room temperature thereaction mixture was concentrated to yield (R)-methyl2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylateas its corresponding HCl salt, as a solid; which was directly used intothe next step.

MS m/z 451.0 (M+H)⁺.

STEP G: (R)-Methyl2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of (R)-methyl2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(150 mg, 0.334 mmol) in DCM (10 mL) and DIPEA (0.28 mL, 1.67 mmol) wasadded cyclopropanecarbonyl chloride (0.038 mL, 0.40 mmol). Afterstirring at room temperature for 3 h, the reaction mixture waspartitioned between aqueous NaHCO₃ and DCM. The organic phase was washedwith brine, dried over Na₂SO₄, filtered and concentrated in vacuo toyield (R)-methyl2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(130 mg, 75%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.68-0.80 (m, 2H), 0.90-0.99 (m, 2H),1.38-1.64 (m, 5H), 1.72-1.84 (m, 1H), 1.87-2.04 (m, 3H), 2.18-2.44 (m,1H), 2.95 (dd. J=12.0, 7.1 Hz, 1H), 3.13-3.34 (m, 1H), 3.41-3.71 (m,7H), 3.73 (s, 3H), 3.96-4.23 (m, 2H), 7.46 (dd, J=8.3, 5.9 Hz, 2H),7.62-7.73 (m, 2H); MS m/z 517.0 (M+H)⁺.

STEP H: (R)-Methyl2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(Compound #14)

To a solution of (R)-methyl2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(50 mg, 0.097 mmol) and benzofuran-5-ylboronic acid (24.0 mg, 0.145 mol)in DME (2 mL) was added under argon aqueous 2M Na₂CO₃ (0.1 mL, 0.20mmol) and Pd(PPh₃)₄ (3.4 mg, 0.003 mmol). The reaction mixture wasrefluxed for 16 h, filtered, concentrated in vacuo and the resultingresidue was purified by flash chromatography (silica gel, 2.5% MeOH/DCM)to yield (R)-methyl2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate(45 mg, 84%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.71 (dd, J=7.6, 2.9 Hz, 2H), 0.89-0.96(m, 2H), 1.38-1.68 (m, 4H), 1.82 (dd, J=11.5, 5.1 Hz, 1H), 1.89-2.09 (m,3H), 2.38-2.54 (m, 1H), 3.00 (dd, J=12.0, 7.1 Hz, 1H), 3.15-3.35 (m,1H), 3.42-3.70 (m, 5H), 3.71-3.78 (m, 4H), 4.15 (br. s., 2H), 6.85 (d,J=2.0 Hz, 1H), 7.53-7.58 (m, 1H), 7.61 (d, J=8.6 Hz, 1H), 7.63-7.72 (m,3H), 7.73-7.81 (m, 2H), 7.84 (s, 1H); MS m/z 555.0 (M+H)⁺.

Following the procedure described in Example 5, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 15

Methyl 3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8- carboxylate ¹H NMR (400 MHz,CDCl₃) δ ppm 0.64- 0.77 (m, 2 H), 0.88-0.99 (m, 2 H), 1.42- 1.64 (m, 4H), 1.77-2.09 (m, 3 H), 2.23- 2.53 (m, 1 H), 2.94-3.34 (m, 1 H), 3.46-3.72 (m, 5 H), 3.72-3.79 (m, 4 H), 3.96- 4.26 (m, 2 H), 6.62 (br. s., 1H), 7.28 (br. s., 1 H), 7.43-7.49 (m, 2 H), 7.63 (t, J = 7.8 Hz, 2 H),7.74-7.83 (m, 2 H), 7.90 (s, 1 H), 8.62 (br. s., 1 H); MS m/z 554.2 (M +H)⁺ 16

Methyl 2-[4-(1-benzofuran-5-yl)phenyl]-3-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4-oxo-1,3,8-triazaspiro[4.5]dec- 1-ene-8-carboxylate ¹H NMR(400 MHz, CDCl₃) δ ppm 0.70 (dd, J = 7.8, 3.4 Hz, 2 H), 0.85-0.94 (m, 2H), 1.22-1.33 (m, 1 H), 1.54 (d, J = 13.2 Hz, 2 H), 1.92-2.06 (m, 2 H),2.75 (br. s., 1 H), 3.44-3.61 (m, 3 H), 3.75 (s, 3 H), 3.84- 4.08 (m, 5H), 4.08-4.24 (m, 2 H), 6.86 (d, J = 2.0 Hz, 1 H), 7.56 (dd, J = 8.6,1.7 Hz, 1 H), 7.62 (d, J = 8.6 Hz, 1 H), 7.65 (d, J = 8.3 Hz, 2 H), 7.70(d, J = 2.0 Hz, 1 H), 7.78 (d, J = 8.3 Hz, 2 H), 7.84 (d, J = 1.5 Hz, 1H); MS m/z 541.0 (M + H)⁺ 17

Methyl 3-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8- carboxylate ¹H NMR (400 MHz,CDCl₃) δ ppm 0.70 (dd, J = 7.8, 3.2 Hz, 2 H), 0.91 (br. s., 2 H), 1.21-1.34 (m, 1 H), 1.54 (d, J = 12.7 Hz, 2 H), 1.90-2.06 (m, 2 H), 2.75 (br.s., 1 H), 3.45- 3.63 (m, 3 H), 3.75 (s, 3 H), 3.82-4.07 (m, 4 H),4.07-4.25 (m, 2 H), 6.64 (br. s., 1 H), 7.29 (t, J = 2.7 Hz, 1 H),7.42-7.51 (m, 2 H), 7.62 (m, J = 8.3 Hz, 2 H), 7.80 (m, J = 8.1 Hz, 2H), 7.91 (s, 1 H), 8.56 (br. s., 1 H); MS m/z 540.3 (M + H)⁺

Example 6(R)-2-(4-(1H-Indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #63)

and(R)-2-(4-(1H-indol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl-8-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #81)

STEP A: 4-Amino-1-benzylpiperidine-4-carbonitrile

To a solution of ammonium chloride (17.3 g, 323 mmol) in water (200 mL)was added successively aqueous 25% ammonia (25 mL, 332 mmol) and1-benzylpiperidin-4-one (11.43 g, 60 mmol). The resulting mixture wasstirred at room temperature for 20 min and sodium cyanide (14.7 g, 300mmol) was added in portions over 15 min. After stirring for 1 day, thereaction mixture was partitioned between water (200 mL) and DCM (2×200mL). The organic phase was dried over MgSO₄, filtered and concentratedin vacuo to yield a residue. The residue was purified by flashchromatography (silica gel, 50% EtOAc/heptanes to 100% EtOAc) to yield4-amino-1-benzylpiperidine-4-carbonitrile (6.15 g, 47%).

¹H NMR (300 MHz, CDCl₃) δ ppm 1.69-1.86 (m, 4H), 2.00 (dt, J=13.1, 2.1Hz, 2H), 2.27-2.45 (m, 2H), 2.83 (dt, J=12.4, 3.6 Hz, 2H), 3.55 (s, 2H),7.21-7.39 (m, 5H); MS m/z 216 (M+H)⁺.

STEP B: 4-Amino-1-benzylpiperidine-4-carboxamide

To a solution of 4-amino-1-benzylpiperidine-4-carbonitrile (6.15 g, 28.6mmol) in DCM (70 mL) at −5° C. was added 95-97% sulfuric acid (50 mL).The reaction mixture was stirred at 0 to 5° C. overnight and the organiclayer was discarded. The resulting mixture was poured onto crushed ice(1000 mL) and the pH adjusted to pH 9 with aqueous 5N NaOH, keeping thetemperature below 10° C. The resulting mixture was partitioned betweenwater and EtOAc (3×500 mL). The organic phase was dried over MgSO₄,filtered and concentrated in vacuo to yield a residue. The residue waspurified by flash chromatography (silica gel, 5% MeOH in DCM) to yield2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (5.06 g, 76%).

¹H NMR (300 MHz, CDCl₃) δ ppm 1.29-1.57 (m, 4H), 2.14-2.39 (m, 4H),2.71-2.84 (m, 2H), 3.55 (s, 2H), 5.41 (br. s., 1H), 7.20-7.38 (m, 5H),7.45 (br. s., 1H); MS m/z 234 (M+H)⁺.

STEP C: 1-Benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide

A mixture 4-amino-1-benzylpiperidine-4-carboxamide (2 g, 8.31 mmol),4-bromobenzoic acid (1.67 g, 8.31 mmol), EDCI (1.59 g, 8.31 mmol), HOBt(1.12 g, 8.31 mmol) and DIPEA (1.43 mL, 8.31 mmol) in DMF (45 mL) wasstirred at room temperature for 1 day. The reaction mixture waspartitioned between EtOAc and aqueous saturated NaHCO₃. The organicphase was washed with brine, dried over Na₂SO₄, filtered andconcentrated in vacuo to yield1-benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide (3.4 g, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.74-1.87 (m, 2H), 1.97-2.14 (m, 4H),2.45 (d, J=11.5 Hz, 2H), 3.21 (s, 2H), 3.29 (s, 2H), 6.73 (s, 1H), 6.94(s, 1H), 7.04-7.23 (m, 5H), 7.54 (d, J=8.3 Hz, 2H), 7.67 (d, J=8.6 Hz,2H), 7.91 (s, 1H); MS m/z 418.0 (M+H)⁺.

STEP D: 8-Benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

A mixture of 1-benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide (2 g,4.8 mmol) and NaOH (0.96 g, 24.0 mmol) in H₂O (4.81 mL) and MeOH (80 mL)was stirred at 65° C. for 1 day. The reaction mixture was partitionedbetween water (300 mL) and EtOAc (2×300 mL). The organic phase waswashed with brine, dried over Na₂SO₄, filtered and concentrated in vacuoto yield 8-benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(1.56 g, 82%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.36-1.54 (m, 2H), 1.76-1.90 (m, 2H),2.42-2.45 (m, 2H), 2.70-2.82 (m, 2H), 3.56 (s, 2H), 7.21-7.28 (m, 1H),7.30-7.37 (m, 4H), 7.75 (d, J=7.8 Hz, 2H), 7.90 (br. s., 2H); MS m/z400.0 (M+H)⁺.

STEP E: (S)-tert-Butyl3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate

To a stirring solution of8-benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.95 g,2.38 mmol) and (R)-tert-butyl 3-(iodomethyl)pyrrolidine-1-carboxylate(1.33 g, 4.77 mmol) in DMF (10 mL) was added K₂CO₃ (0.66 g, 4.77 mmol).After stirring at 65° C. for 48 h, the reaction mixture was partitionedbetween water and EtOAc. The organic phase was washed with brine, driedover MgSO₄, filtered and concentrated in vacuo to yield a residue. Theresidue was purified by flash chromatography (silica gel, 2-5% MeOH/DCM)to yield (S)-tert-butyl3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate(0.75 g, 57%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.17 (br. s., 1H), 1.41 (s, 9H), 1.46-1.56(m, 2H), 1.67-1.82 (m, 2H), 1.87-2.02 (m, 2H), 2.23 (d, J=6.8 Hz, 1H),2.71-2.87 (m, 1H), 3.09-3.39 (m, 2H), 3.47 (s, 3H), 3.53-3.68 (m, 2H),3.72 (s, 3H), 3.94-4.20 (m, 2H), 7.45 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.1Hz, 2H); MS n/z 540.0 (M+H)⁺.

STEP F:(R)-8-Benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (S)-tert-butyl3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate(5.05 g, 8.68 mmol) in 1,4-dioxane (20 mL) was added 4M HCl in1,4-dioxane (20 mL). After stirring for 4 h at room temperature thereaction mixture was diluted with diethyl ether; the precipitate wasfiltered off, washed with diethyl ether and dried to yield(R)-8-benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,as its corresponding bis-HCl salt (5.06 g, 95%).

MS m/z 481.0 (M+H)⁺.

STEP G:(R)-8-Benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of(R)-8-benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(5.05 g, 8.66 mmol) in DCM (100 mL) and triethylamine (6.04 mL, 43.3mmol) was added at 0° C. cyclopropanecarbonyl chloride (0.87 mL, 9.53mmol). After stirring at room temperature for 1 h, MeOH (5 mL) was addedto the solution and the reaction mixture was partitioned between aqueous1M NaOH and DCM. The organic phase was dried over MgSO₄, filtered andconcentrated in vacuo to yield((R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(4.94 g, 99%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.68-0.80 (m, 2H), 0.90-0.99 (m, 2H),1.38-1.64 (m, 5H), 1.72-1.84 (m, 1H), 1.87-2.04 (m, 3H), 2.18-2.44 (m,1H), 2.95 (dd, J=12.0, 7.1 Hz, 1H), 3.13-3.34 (m, 1H), 3.41-3.71 (m,7H), 3.73 (s, 3H), 3.96-4.23 (m, 2H), 7.46 (dd, J=8.3, 5.9 Hz, 2H),7.62-7.73 (m, 2H); MS m/z 549.0 (M+H)⁺.

STEP H:(R)-2-(4-(1H-Indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #63)

((R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.382 g, 0.695 mmol), 1H-indol-5-yl-5-boronic acid (0.134 g, 0.834mmol), tetrakis(triphenylphosphine) palladium (0.040 g, 0.035 mmol),potassium carbonate (0.192 g, 0.241 mmol), dioxane (25 mL) and water (2mL) were combined and the resulting mixture was heated at reflux for 16h. The mixture was diluted with water and extracted with ethyl acetate.The extracts were concentrated to a dark oil, which was purified byflash chromatography (silica gel, 0 to 5% methanol in dichloromethane)to yield(R)-2-(4-(1H-indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one as aslightly pink solid (0.183 g)

¹H NMR (400 MHz, CDCl₃) δ ppm 0.67-0.73 (m, 2H), 0.89-0.97 (m, 2H),1.39-1.66 (m, 3H), 1.75-2.02 (m, 2H), 2.08-2.21 (m, 2H), 2.28-2.51 (m,1H), 2.68 (t, J=11.1 Hz, 2H), 2.83-2.95 (m, 1H), 3.02 (dd, J=12.1, 7.1Hz, 1H), 3.13-3.34 (m, 1H), 3.43-3.76 (m, 7H), 6.61 (br. s., 1H),7.22-7.29 (m, 2H), 7.30-7.39 (m, 4H), 7.44 (d, J=8.6 Hz, 2H), 7.61 (t,J=8.1 Hz, 2H), 7.77 (dd, J=10.1, 8.1 Hz, 2H), 7.89 (s, 1H), 8.73 (d,J=7.1 Hz, 1H) MS m/z 586.3 (M+H)⁺.

STEP I:(R)-2-(4-(1H-Indol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-methy-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #81)

(R)-2-(4-(1H-indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.050 g,0.085 mmol) was dissolved in a mixture of formic acid (0.5 mL) inmethanol (5 mL). 10% palladium on carbon (0.005 g) was added. Theresulting mixture was heated at reflux for 16 h. The mixture was thendiluted with brine and extracted 3 times with ethyl acetate. Thecombined ethyl acetate extracts were washed with saturated aqueoussodium bicarbonate, filtered through diatomaceous earth, andconcentrated under vacuum. The resulting oil was purified by flashchromatography (silica gel, 0 to 5% methanol in dichloromethane) toyield(R)-2-(4-(1H-Indol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-oneas a white solid (0.003 g).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.60-0.78 (m, 2H), 0.84-0.97 (m, 2H),1.15-1.33 (m, 1H), 1.37-1.56 (m, 2H), 1.75-1.99 (m, 1H), 2.05-2.21 (m,2H), 2.27-2.52 (m, 4H), 2.64 (t, J=10.8 Hz, 2H), 2.74-2.90 (m, 2H), 3.02(dd, J=12.0, 6.8 Hz, 1H), 3.13-3.33 (m, 1H), 3.61 (m, J=13.4 Hz, 5H),6.64 (t, J=2.2 Hz, 0H), 7.19-7.34 (m, 1H), 7.41-7.55 (m, 2H), 7.60-7.66(m, 2H), 7.79 (dd, J=8.3, 6.4 Hz, 2H), 7.90 (s, 1H), 8.34 (br. s., 1H)MS m/z 510.0 (M+H)⁺.

Following the procedure described in Example 6, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundof formula (I) of the invention was prepared.

ID No. Structure Compound Name & Physical Data 193

8-Benzyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.76 (m, 2 H), 0.84-1.01 (m, 2 H), 1.36- 1.71 (m, 3 H), 1.71-2.00 (m, 2H), 2.07- 2.26 (m, 2 H), 2.26-2.56 (m, 1 H), 2.68 (t, J = 10.7 Hz, 2 H),2.78-3.06 (m, 3 H), 3.12-3.40 (m, 1 H), 3.41-3.84 (m, 6 H), 7.20-7.43(m, 5 H), 7.67-7.77 (m, 3 H), 7.80-7.95 (m, 3 H), 8.01-8.16 (m, 2 H),8.60 (d, J = 5.8 Hz, 1 H), 9.32 (s, 1 H); MS m/z 554.2 (M + H)⁺

Example 7(R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenol)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #128)

and(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #139)

STEP A:(R)-2-(4-Bromophenyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring suspension of(R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(4.94 g, 8.54 mmol) and potassium bicarbonate (10.26 g, 102.5 mmol) inDCM (100 mL) was added 1-chloroethyl chloroformate (2.65 mL, 24.6 mmol).After refluxing for 1.5 h the reaction mixture was filtered and thefiltrate concentrated in vacuo. The residue was dissolved in MeOH (100mL) and the solution was refluxed for 1 h, cooled down to roomtemperature and concentrated in vacuo. The residue was triturated withdiethyl ether and the solid was filtered and dried to yield(R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(4.5 g, 99%).

MS m/z 459.0 (M+H)⁺.

STEP B:(R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #128)

(R)-2-(4-Bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(1 g, 1.9 mmol),1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole(0.652 g, 2.28 mmol), aqueous 1.0M Na₂CO₃ (4 mL, 4 mmol) andacetonitrile (20 mL) were combined and bubbled with nitrogen for 15 min.Bis(triphenylphosphine)palladium (II) chloride (0.067 g, 0.095 mmol) wasadded and the mixture was heated at 85° C. for 1.5 h. The resultingmixture was diluted with water and extracted with DCM.

The extracts were concentrated to yield a residue which was purified byflash chromatography (silica gel, DCM/MeOH/NH₄OH 910.910.1) to yield(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.573 g, 54%).

¹H NMR (300 MHz, DMSO-d6) δ ppm 0.56-0.71 (m, 4H), 1.26-2.04 (m, 7H),2.05-2.39 (m, 1H), 2.74-3.60 (m, 9H), 3.65 (t, J=6.9 Hz, 2H), 4.09 (s,3H), 7.71-7.85 (m, 4H), 7.86-7.95 (m, 2H), 8.08-8.19 (m, 2H); MS m/z511.0 (M+H)⁺.

STEP C:(R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #139)

To a stirring solution of(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(80 mg, 0.147 mmol) in DCM (5 mL) and Et₃N (0.20 mL, 1.43 mmol) wasadded isobutyryl chloride (0.019 mL, 0.176 mmol). After stirring at roomtemperature for 1 h, the reaction mixture was quenched with MeOH (0.5mL) and partitioned between aqueous 1.0 M NaOH and DCM. The organicphase was dried over MgSO₄, filtered and concentrated in vacuo to yielda residue which was purified by flash chromatography (silica gel, 0 to7.5% MeOH in DCM) and re-purified by reverse phase prep-HPLC to yield(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(74 mg, 86%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (d, J=4.7 Hz, 2H), 0.79-1.05 (m, 2H),1.14-1.25 (m, 6H), 1.27-2.14 (m, 8H), 2.14-2.61 (m, 1H), 2.71-3.10 (m,2H), 3.10-3.84 (m, 6H), 3.86-4.08 (m, 1H), 4.06-4.21 (m, 3H), 4.52 (br.s., 1H), 7.51 (d, J=8.8 Hz, 1H), 7.61-7.75 (m, 3H), 7.75-7.85 (m, 2H),7.97 (s, 1H), 8.07 (s, 1H); MS nm/z 581.0 (M+H)⁺; m.p. 104.2° C.

Following the procedure described in Example 7, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 106

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.2 Hz, 4 H),1.25-2.00 (m, 7 H), 2.01-2.40 (m, 1 H), 2.76- 3.76 (m, 11 H), 7.87 (dd,J = 8.1, 4.9 Hz, 2 H), 7.93 (d, J = 5.8 Hz, 1 H), 7.97-8.17 (m, 3 H),8.26 (d, J = 8.7 Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J = 5.8 Hz, 1 H),9.37 (s, 1 H); MS m/z 508 (M + H)⁺ 130

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one MS m/z 483 (M + H)⁺ 131

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 497(M + H)⁺ 132

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one MS m/z 494 (M + H)⁺ 133

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz,DMSO-d6) δ ppm 0.53-0.72 (m, 4 H), 1.25-1.93 (m, 5 H), 2.08-2.40 (m, 1H), 2.74-3.59 (m, 10 H), 3.65 (t, J = 6.9 Hz, 2 H), 4.08 (br. s., 1 H),6.98-7.08 (m, 1 H), 7.62-7.83 (m, 4 H), 7.83-7.93 (m, 2 H), 7.99-8.09(m, 2 H); MS m/z 497 (M + H)⁺ 155

3-{[(3R_=1= (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.53-0.70(m, 4 H), 1.22-1.95 (m, 6 H), 2.03-2.39 (m, 1 H), 2.48 (s, 3 H),2.76-3.27 (m, 7 H), 3.36-3.59 (m, 3 H), 3.58-3.72 (m, 2 H), 6.66 (s, 1H), 7.60 (s, 2 H), 7.70-7.82 (m, 2 H), 7.82-7.92 (m, 3 H); MS m/z 511(M + H)⁺ m.p. 95.5° C. 138

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,CDCl₃) δ ppm 0.72 (dd, J = 7.5, 3.2 Hz, 2 H), 0.94 (br. s., 2 H),1.32-1.68 (m, 4 H), 1.74-2.12 (m, 3 H), 2.16 (s, 3 H), 2.34-2.58 (m, 1H), 2.80-3.99 (m, 9 H), 4.13 (s, 3 H), 4.37-4.59 (m, 1 H), 7.51 (d, J =8.7 Hz, 1 H), 7.80 (dd, J = 8.2, 3.9 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s, 1H); MS m/z 553 (M + H)⁺ m.p. 111.2° C. 140

8-(Cyclopropylcarbonyl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,CDCl₃) δ ppm 0.63-0.76 (m, 2 H), 0.76-0.88 (m, 2 H), 0.88-0.99 (m, 2 H),1.04 (br. s., 2 H), 1.36-1.56 (m, 2 H), 1.71-2.63 (m, 6 H), 2.85-3.95(m, 9 H), 4.14 (s, 3 H), 4.17-4.33 (m, 1 H), 4.37- 4.59 (m, 1 H), 7.51(d, J = 8.7 Hz, 1 H), 7.69 (d, J = 8.8 Hz, 3 H), 7.75- 7.86 (m, 2 H),7.98 (s, 1 H), 8.07 (s, 1 H); MS m/z 579 (M + H)⁺ m.p. 114.8° C. 141

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71(d, J = 4.4 Hz, 2 H), 0.93 (br. s., 2 H), 1.35-1.76 (m, 4 H), 1.74-2.13(m, 4 H), 2.31 (s, 6 H), 2.35-2.59 (m, 1 H), 2.85-3.86 (m, 9 H), 4.04-4.18 (m, 1 H), 4.13 (s, 3 H), 4.31- 4.55 (m, 1 H), 7.50 (d, J = 8.7 Hz,1 H), 7.61-7.74 (m, 3 H), 7.74-7.86 (m, 2 H), 7.97 (s, 1 H), 8.06 (s, 1H); MS m/z 596 (M + H)⁺ m.p. 127.5° C. 142

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2- (4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (dt, J= 4.9, 2.4 Hz, 2 H), 0.84- 1.03 (m, 2 H), 1.33-2.14 (m, 9 H), 2.33 (s, 6H), 2.36-2.63 (m, 1 H), 2.85-3.99 (m, 8 H), 4.03-4.32 (m, 1 H),4.30-4.60 (m, 1 H), 7.64-7.83 (m, 3 H), 7.89 (dd, J = 8.7, 2.1 Hz, 3 H),7.99-8.19 (m, 2 H), 8.60 (d, J = 5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 593(M + H)⁺ m.p. 94.2° C. 143

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-8-(2-methylpropanoyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm0.61-0.80 (m, 2 H), 0.83-1.02 (m, 2 H), 1.13-1.27 (m, 6 H), 1.35-1.71(m, 4 H), 1.86-2.14 (m, 3 H), 2.18- 2.62 (m, 1 H), 2.87 (dt, J = 13.5,6.7 Hz, 1 H), 2.92-3.89 (m, 9 H), 3.98 (d, J = 12.0 Hz, 1 H), 4.50 (d, J= 12.4 Hz, 1 H), 7.75 (d, J = 7.8 Hz, 3 H), 7.89 (dd, J = 8.6, 2.0 Hz, 2H), 7.97- 8.20 (m, 2 H), 8.61 (br. s., 1 H), 9.34 (br. s., 1 H); MS m/z578 (M + H)⁺ m.p. 129.9° C. 144

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.65-0.80 (m, 2 H), 0.83-1.02 (m,2 H), 1.36-1.69 (m, 4 H), 1.88-2.13 (m, 3 H), 2.17 (s, 3 H), 2.20-2.61(m, 1 H), 2.79-4.01 (m, 9 H), 4.38- 4.56 (m, 1 H), 7.68-7.82 (m, 3 H),7.84-7.96 (m, 3 H), 8.01-8.16 (m, 2 H), 8.60 (d, J = 5.5 Hz, 1 H), 9.33(br. s., 1 H); MS m/z 550 (M + H)⁺ m.p. 123.1° C. 134

2-[4-(1-Benzofuran-5-yl)phenyl]-8- (cyclopropylcarbonyl)-3-{[1-(cyclopropylcarbonyl)azetidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.70 (m, 4 H), 1.25-1.93(m, 7 H), 2.08-2.39 (m, 1 H), 2.75-3.03 (m, 4 H), 3.03-3.59 (m, 6 H),3.65 (t, J = 6.9 Hz, 2 H), 4.08 (br. s., 1 H), 7.04 (d, J = 1.6 Hz, 1H), 7.61-7.83 (m, 4 H), 7.82-7.93 (m, 2 H), 8.00-8.11 (m, 2 H); MS m/z551 (M + H)⁺ m.p. 93.6° C. 149

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(N,N-dimethylglycyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one¹H NMR (300 MHz, DMSO-d6) δ ppm 0.56-0.68 (m, 4 H), 1.14-1.30 (m, 3 H),1.30-1.43 (m, 1 H), 1.44-1.60 (m, 2 H), 1.62-1.79 (m, 1 H), 1.79- 1.99(m, 1 H), 2.35 (s, 6 H), 2.55- 2.71 (m, 1 H), 3.13-3.27 (m, 2 H),3.67-3.81 (m, 2 H), 3.88 (d, J = 7.3 Hz, 2 H), 3.96 (d, J = 13.3 Hz, 1H), 4.13 (t, J = 8.2 Hz, 1 H), 4.28 (d, J = 12.9 Hz, 1 H), 7.04 (d, J =1.9 Hz, 1 H), 7.65-7.76 (m, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.90 (m, J= 8.2 Hz, 2 H), 7.96-8.12 (m, 2 H); MS m/z 568 (M + H)⁺ m.p. 130.1° C.150

8-Acetyl-2-[4-(1-benzofuran-5- yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz,DMSO-d6) δ ppm 0.63 (d, J = 5.6 Hz, 4 H), 1.41-1.95 (m, 6 H), 2.07 (s, 3H), 2.1-2.3 (m, 1 H), 2.77-2.92 (m, 0.5 H), 2.96-3.30 (m, 3.5 H),3.36-3.60 (m, 3 H), 3.66 (t, J = 7.1 Hz, 2 H), 3.86 (d, J = 13.7 Hz, 1H), 4.29 (d, J = 12.9 Hz, 1 H), 7.04 (d, J = 1.8 Hz, 1 H), 7.65-7.76 (m,2 H), 7.76-7.85 (m, 2 H), 7.85-7.92 (m, 2 H), 7.97-8.10 (m, 2 H); MS m/z539 (M + H)⁺ m.p. 96.6° C. 151

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-methylpropanoyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm0.63 (d, J = 5.5 Hz, 4 H), 0.94-1.11 (m, 6 H), 1.42-1.94 (m, 6 H), 2.10-2.41 (m, 1 H), 2.74-3.29 (m, 5 H), 3.37-3.62 (m, 3 H), 3.61-3.72 (m, 2H), 3.98 (d, J = 13.5 Hz, 1 H), 4.32 (d, J = 11.7 Hz, 1 H), 7.04 (d, J =1.8 Hz, 1 H), 7.63-7.76 (m, 2 H), 7.76-7.85 (m, 2 H), 7.85-7.95 (m, 2H), 7.99- 8.11 (m, 2 H); MS m/z 567 (M + H)⁺ m.p. 105.5° C. 152

2-[4-(1-Benzofuran-5-yl)phenyl]-8- (cyclopropylcarbonyl)-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz,DMSO-d6) δ ppm 0.51-0.68 (m, 4 H), 0.68-0.89 (m, 4 H), 1.38-1.94 (m, 7H), 1.95-2.11 (m, 1 H), 2.11-2.40 (m, 1 H), 2.77- 2.95 (m, 0.5 H), 3.11(m, 2.5 H), 3.39- 3.77 (m, 5 H), 4.15-4.39 (m, 2 H), 7.04 (s, 1 H),7.65-7.77 (m, 2 H), 7.77-7.85 (m, 2 H), 7.85-7.98 (m, 2 H), 7.98-8.14(m, 2 H); MS m/z 565 (M + H)⁺ m.p. 115.1° C. 153

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm0.55-0.72 (m, 4 H), 1.42-1.97 (m, 6 H), 2.22 (s, 6 H), 2.24-2.41 (m, 1H), 2.86 (dd, J = 12.0, 7.4 Hz, 0.5 H), 2.97- 3.29 (m, 5.5 H), 3.37-3.62(m, 3 H), 3.62-3.73 (m, 2 H), 4.07 (d, J = 13.1 Hz, 1 H), 4.29 (d, J =12.8 Hz, 1 H), 7.05 (d, J = 1.6 Hz, 1 H), 7.66- 7.77 (m, 2 H), 7.77-7.85(m, 2 H), 7.85-7.96 (m, 2 H), 8.00-8.12 (m, 2 H); MS m/z 582 (M + H)⁺m.p. 92° C. 135

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-(2- methylpropanoyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 567 (M + H)⁺ m.p. 160.8° C. 136

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 582 (M + H)⁺ m.p. 102.3° C.137

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-8-(2-methylpropanoyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d6) δ ppm 0.50-0.72 (m, 4 H), 0.91-1.16 (m, 6 H),1.31-1.44 (m, 1 H), 1.44-1.91 (m, 4 H), 2.54-2.71 (m, 1 H), 2.85- 3.02(m, 1 H), 3.08-3.27 (m, 1 H), 3.34-3.42 (m, 1 H), 3.46-3.66 (m, 1 H),3.66-3.81 (m, 2 H), 3.88 (d, J = 7.4 Hz, 2 H), 3.98 (d, J = 12.6 Hz, 1H), 4.09-4.22 (m, 1 H), 4.32 (d, J = 13.2 Hz, 1 H), 7.83-7.97 (m, 3 H),8.01-8.18 (m, 3 H), 8.27 (d, J = 8.7 Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J= 5.8 Hz, 1 H), 9.38 (s, 1 H); MS m/z 564 (M + H)⁺ m.p. 157.5° C. 154

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2- (4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.71(m, 4 H), 1.29-1.43 (m, 1 H), 1.43-1.62 (m, 2 H), 1.62-1.78 (m, 1 H),1.87 (t, J = 9.8 Hz, 1 H), 2.21 (s, 6 H), 2.55-2.71 (m, 1 H), 2.96- 3.27(m, 3 H), 3.43-3.62 (m, 2 H), 3.65-3.82 (m, 2 H), 3.88 (d, J = 7.3 Hz, 2H), 4.06 (d, J = 13.5 Hz, 1 H), 4.15 (t, J = 8.2 Hz, 1 H), 4.27 (d, J =12.8 Hz, 1 H), 7.82-7.99 (m, 3 H), 7.99-8.16 (m, 3 H), 8.27 (d, J = 8.7Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J = 5.8 Hz, 1 H), 9.38 (s, 1 H); MSm/z 579 (M + H)⁺ m.p. 233.0° C. 171

8-(Cyclopropylcarbonyl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61-0.76(m, 2 H), 0.76-0.85 (m, 2 H), 0.86-0.99 (m, 2 H), 0.99-1.09 (m, 2 H),1.36-2.17 (m, 9 H), 2.50 (s, 3 H), 2.89-3.99 (m, 8 H), 4.09- 4.34 (m, 1H), 4.34-4.61 (m, 1 H), 6.45 (s, 1 H), 7.36-7.58 (m, 2 H), 7.59-7.74 (m,3 H), 7.73-7.88 (m, 2 H); MS m/z 579 (M + H)⁺ m.p. 137.1° C. 172

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-8-(2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz,CDCl₃) δ ppm ppm 0.64-0.80 (m, 2 H), 0.85-1.01 (m, 2 H), 1.03-1.25 (m,10 H), 1.35- 2.12 (m, 6 H), 2.50 (s, 3 H), 2.72- 3.86 (m, 7 H),3.86-4.06 (m, 1 H), 4.37-4.62 (m, 1 H), 6.44 (s, 1 H), 7.38-7.56 (m, 2H), 7.58-7.73 (m, 3 H), 77.3-7.84 (m, 2 H); MS m/z 581 (M + H)⁺ m.p.115.5° C. 174

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2- [4-(2-methyl-1-benzofuran-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, CDCl₃)δ ppm 0.55-0.78 (m, 2 H), 0.82-1.03 (m, 2 H), 1.35-1.73 (m, 4 H),1.72-2.13 (m, 3 H), 2.31 (s, 6 H), 2.49 (s, 3 H), 2.89-3.87 (m, 11 H),4.05-4.21 (m, 1 H), 4.30-4.55 (m, 1 H), 6.44 (s, 1 H), 7.38-7.56 (m, 2H), 7.58-7.72 (m, 3 H), 7.72-7.83 (m, 2 H); MS m/z 596 (M + H)⁺ m.p.90.3° C. 181

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d,J = 5.4 Hz, 4 H), 1.31- 1.94 (m, 6 H), 2.07 (s, 3 H), 2.37 (s, 3 H),2.50 (s, 3 H), 2.78-3.30 (m, 4 H), 3.32-3.60 (m, 4 H), 3.60-3.74 (m, 2H), 3.77-3.93 (m, 1 H), 4.18-4.38 (m, 1 H), 7.68 (d, J = 8.7 Hz, 1 H),7.75-7.89 (m, 2 H), 7.90-8.07 (m, 4 H); MS m/z 583 (M + H)⁺ m.p. 117.7°C. 182

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(N,N-dimethylglycyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.64 (d, J = 5.4 Hz, 4 H), 1.28- 1.97 (m, 7 H), 2.21 (s,6 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.76-3.28 (m, 6 H), 3.34-3.61 (m, 3H), 3.60-3.75 (m, 2 H), 3.95-4.14 (m, 1 H), 4.18- 4.37 (m, 1 H), 7.68(d, J = 7.8 Hz, 1 H), 7.75-7.90 (m, 2 H), 7.97 (d, J = 8.9 Hz, 4 H); MSm/z 626 (M + H)⁺ m.p. 107.9° C. 183

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.51-0.71 (m, 4 H), 0.94-1.13 (m, 6 H), 1.28-1.99 (m, 6H), 2.12-2.35 (m, 1 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.76-3.30 (m, 5H), 3.33-3.78 (m, 5 H), 3.84-4.12 (m, 1 H), 4.19-4.43 (m, 1 H), 7.68 (d,J = 8.9 Hz, 1 H), 7.82 (dd, J = 8.0, 5.4 Hz, 2 H), 7.97 (d, J = 8.7 Hz,4 H); MS m/z 611 (M + H)⁺ m.p. 136.4° C.

Example 8(R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-(2-hydroxyethyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #127)

A mixture of(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.080 g, 0.157 mmol), 2-bromoethanol (0.056 mL, 0.785 mmol), andpotassium carbonate (0.044 g, 0.314 mmol) in acetonitrile (5 mL) washeated at 65° C. overnight. The resulting mixture was allowed to cool toroom temperature and was diluted with DCM (20 mL). The inorganic solidswere filtered and the filtrate was concentrated yield a residue. Theresidue was purified by flash chromatography (silica gel, 0 to 100% ofDCM:MeOH: 25% NH₄OH 9:0.9:0.1 in DCM). The fractions containing thedesired product were concentrated to a sticky oil that was trituratedwith Et₂O to yield3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one,as an off-white solid (0.042 g, 48%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.60-0.82 (m, 2H), 0.82-1.03 (m, 2H),1.33-2.61 (m, 10H), 2.61-3.11 (m, 6H), 3.09-3.85 (m, 7H), 4.13 (s, 3H),7.50 (d, J=8.7 Hz, 1H), 7.58-7.72 (m, 3H), 7.72-7.85 (m, 2H), 7.97 (s,1H), 8.06 (s, 1H); MS m/z 555 (M+H)⁺; m.p. 99.6° C.;

Following the procedure described in Example 8, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 159

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-(4- isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.76(m, 2 H), 0.89-1.00 (m, 2 H), 1.37-1.71 (m, 4 H), 1.73-2.23 (m, 6 H),2.23-2.58 (m, 1 H), 2.69 (t, J = 5.2 Hz, 2 H), 2.79 (t, J = 11.1 Hz, 2H), 2.86-3.07 (m, 3 H), 3.14-3.39 (m, 1 H), 3.57-3.85 (m, 5 H), 7.67-7.80 (m, 3 H), 7.88 (dd, J = 8.2, 3.8 Hz, 3 H), 7.99-8.17 (m, 2 H), 8.60(d, J = 5.5 Hz, 1 H), 9.32 (br. s., 1 H); MS m/z 552 (M + H)⁺ 168

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.72(m, 4 H), 1.41-2.00 (m, 7 H), 2.09-2.38 (m, 1 H), 2.52-2.64 (m, 2 H),2.74-2.93 (m, 3 H), 3.02- 3.28 (m, 3 H), 3.39-3.72 (m, 7 H), 4.41 (br.s., 1 H), 7.04 (d, J = 1.8 Hz, 1 H), 7.63-7.82 (m, 4 H), 7.83-7.92 (m, 2H), 8.03 (s, 1 H), 8.06 (d, J = 1.9 Hz, 1 H); MS m/z 541 (M + H)⁺ m.p.105.7° C. 170

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4- (1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 541 (M + H)⁺ m.p. >300° C.173

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4-(2- methyl-1-benzofuran-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm0.63-0.78 (m, 2 H), 0.94 (br. s., 2 H), 1.34-1.56 (m, 2 H), 1.70-2.46(m, 7 H), 2.50 (s, 3 H), 2.58-3.10 (m, 6 H), 3.10-3.39 (m, 1 H), 3.38-3.91 (m, 8 H), 6.44 (s, 1 H), 7.37- 7.56 (m, 2 H), 7.56-7.86 (m, 5 H);MS m/z 555 (M + H)⁺ m.p. 130.3° C. 185

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-hydroxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.72 (m, 4 H), 1.38 (br. s., 1 H),1.81 (br. s., 2 H), 2.18-2.45 (m, 2 H), 2.57-2.72 (m, 1 H), 3.18-3.96(m, 14 H), 4.11-4.21 (m, 1 H), 7.04 (d, J = 1.5 Hz, 1 H), 7.66-7.76 (m,2 H), 7.76-7.86 (m, 2 H), 7.87-7.98 (m, 2 H), 8.00-8.11 (m, 2 H), 10.40(br. s., 1 H); MS m/z 527 (M + H)⁺ m.p. 253.4° C.

Example 9(R)-2-(4-(1H-Indol-5-yl)phenyl)-8-acetyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #147)

STEP A:(R)-8-Acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of(R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.300 mg, 0.605 mmol) and Et₃N (0.252 mL, 1.82 mmol) in DCM (10 mL) wasadded acetyl chloride (0.065 mL, 0.908 mmol). After 1 h at roomtemperature, the resulting mixture was diluted with DCM (50 mL) and waswashed with 0.5 M aqueous Na₂CO₃. The aqueous layer was extracted withadditional DCM (10 mL) and the combined organic layers were dried overMgSO₄, filtered, and concentrated to yield a residue which was purifiedby flash chromatography on Silica gel using 0 to 4.7% MeOH/DCM. Theresulting residue was triturated with di-isopropyl ether to yield(R)-8-acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-oneas a white solid (0.165 g, 53%).

MS m/z 501 (M+H)⁺.

STEP B:8-Acetyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #147)

(R)-8-Acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.075 g, 0.150 mmol), 5-indolylboronic acid (0.029 g, 0.180 mmol), 1.0M aqueous Na₂CO₃ (0.30 mL, 0.30 mmol) and 1,4-dioxane (2 mL) werecombined and bubbled with nitrogen for 15 min.Bis(triphenylphosphine)palladium(II) chloride (0.006 g, 0.008 mmol) wasadded and the resulting mixture was heated to 85° C. for 2 h. Theresulting mixture was cooled to room temperature, diluted with DCM (50mL), and washed successively with water (15 mL) and saturated aqueousNaCl. The organic layer was dried over MgSO₄, filtered, and concentratedto yield a residue which was purified by flash chromatography (silicagel, 0 to 10% MeOH/DCM). The resulting residue was triturated withdi-isopropyl ether to yield8-acetyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one,as a white solid, (0.040 g, 47%).

¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.72 (m, 4H), 1.28-1.95 (m, 6H),2.07 (s, 3H), 2.13-2.39 (m, 1H), 2.86 (dd, J=11.7, 7.0 Hz, 0.5H),3.01-3.30 (m, 3.5H), 3.37-3.62 (m, 3H), 3.62-3.75 (m, 2H), 3.75-3.93 (m,1H), 4.15-4.40 (m, 1H), 6.52 (br. s., 1H), 7.40 (t, J=2.7 Hz, 1H),7.44-7.56 (m, 2H), 7.71-7.81 (nm, 2H), 7.82-7.90 (m, 2H), 7.93 (s, 1H),11.21 (br. s., 1H); MS m/z 538 (M+H)⁺; m.p. 291.7° C.

Following the procedure described in Example 9, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 148

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm0.54-0.74 (m, 4 H), 1.31-1.96 (m, 6 H), 2.07 (s, 3 H), 2.12-2.41 (m, 1H), 2.78- 2.96 (m, 0.5 H), 2.96-3.61 (m, 6.5 H), 3.67 (t, J = 6.9 Hz, 2H), 3.76-3.94 (m, 1 H), 4.30 (d, J = 13.6 Hz, 1 H), 7.61-7.72 (m, 1 H),7.71-7.86 (m, 3 H), 7.86-7.98 (m, 2 H), 8.03-8.33 (m, 2 H), 13.18 (s, 1H) MS m/z 539 (M + H)⁺ m.p. 187.3° C. 129

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.68 (m, 4 H), 0.92-1.10 (m, 6 H),1.27-1.90 (m, 5 H), 2.54-2.71 (m, 1 H), 2.84-3.01 (m, 1 H), 3.17 (t, J =11.1 Hz, 1 H), 3.32-3.80 (m, 4 H), 3.88 (d, J = 7.3 Hz, 2 H), 3.98 (d, J= 13.3 Hz, 1 H), 4.15 (t, J = 8.2 Hz, 1 H), 4.32 (d, J = 12.4 Hz, 1 H),6.92-7.15 (m, 1 H), 7.65-7.76 (m, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.90(d, J = 8.2 Hz, 2 H), 7.99-8.14 (m, 2 H); MS m/z 553 (M + H)⁺ m.p.237.2° C. 164

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(N,N-dimethylflycyl)-2-[4- (1H-indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.73(m, 4 H), 1.27-1.96 (m, 7 H), 2.21 (s, 6 H), 2.23-2.40 (m, 1 H), 2.86(dd, J = 11.5, 6.9 Hz, 0.5 H), 2.97-3.29 (m, 5 H), 3.41-3.61 (m, 2.5 H),3.67 (t, J = 7.0 Hz, 2 H), 4.06 (d, J = 13.5 Hz, 1 H), 4.27 (d, J = 12.6Hz, 1 H), 6.52 (br. s., 1 H), 7.37-7.45 (m, 1 H), 7.45-7.56 (m, 2 H),7.70-7.82 (m, 2 H), 7.82-7.91 (m, 2 H), 7.93 (s, 1 H), 11.21 (br. s., 1H); MS m/z 581 (M + H)⁺ m.p. 129.1° C. 165

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2-[4- (1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (br.s., 4 H), 1.24-2.02 (m, 7 H), 2.20 (br. s., 6 H), 2.24-2.39 (m, 1 H),2.70-3.27 (m, 5 H), 3.39-3.60 (m, 4 H), 3.60-3.79 (m, 2 H), 4.06 (d, J =12.6 Hz, 1 H), 4.28 (d, J = 12.6 Hz, 1 H), 7.57-7.71 (m, 1 H), 7.71-7.85(m, 2 H), 7.85-8.00 (m, 2 H), 8.07-8.26 (m, 2 H), 13.03 (br. s., 1 H);MS m/z 582 (M + H)⁺ m.p. 176.4° C.

Example 10(R)-2-(4-(Benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(Compound #116)

STEP A: (S)-tert-Butyl3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)ethyl)pyrrolidine-1-carboxylate

(S)-ter-Butyl3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate(1.0 g, 2.1 mmol), benzofuran-5-ylboronic acid (0.52 g, 3.15 mmol),tetrakis(triphenylphosphine) palladium (0.073 g, 0.063 mmol), potassiumcarbonate (0.466 g, 4.4 mmol), DME (27 mL) and water (2.2 mL) werecombined and the resulting mixture was heated to reflux for 16 h underargon atmosphere. The resulting mixture was concentrated concentrated invacuo and the residue was purified by flash chromatography (silica gel,10% to 60% EtOAc in heptane) to yield (S)-tert-butyl3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (1.05 g, 98%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.41 (s, 9H), 1.74-1.85 (m, 1H), 1.88-1.99(m, 3H), 1.99-2.13 (m, 6H), 2.26-2.40 (m, 1H), 2.81-2.95 (m, 1H),3.13-3.24 (m, 1H), 3.24-3.32 (m, 1H), 3.33-3.43 (m, 1H), 3.61-3.77 (m,2H), 6.85 (s, 1H), 7.54-7.63 (m, 2H), 7.65 (d, J=7.8 Hz, 2H), 7.69 (s,1H), 7.75 (d, J=8.1 Hz, 2H), 7.85 (s, 1H); MS m/z 514.3 (M+H)⁺.

STEP B:(R)-2-(4-(Benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of (S)-tert-butyl3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (0.9 g, 1.75 mmol) in DCM (36 mL) was addedTFA (9 mL). After stirring 2.5 h at room temperature under nitrogen thereaction mixture was concentrated to yield(R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one,as its corresponding TFA salt, as an oil, which was directly useddirectly into the next step.

MS m/z 414.1 (M+H)⁺.

STEP C:(R)-2-(4-(Benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(Compound #116)

To a stirring solution of(R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-oneTFA salt (41.3 mg, 0.1 mmol) in DCM (2.5 mL) and DIPEA (0.086 mL, 0.5mmol) was added 1-methylcyclopropanecarbonyl chloride (0.014 mg, 0.12mmol). After stirring at room temperature overnight, the reactionmixture was concentrated in vacuo and the resulting residue was purifiedby flash chromatography (silica gel, 25% to 65% EtOAc in heptane) toyield(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (36.5 mg,74%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.44-0.55 (m, 2H), 0.78-1.01 (m, 2H),1.19-1.24 (m, 3H), 1.38-1.64 (m, 2H), 1.78-2.02 (m, 4H), 2.02-2.13 (m,4H), 2.30-2.44 (m, 1H), 3.08 (br. s., 1H), 3.26-3.54 (m, 2H), 3.53-3.84(m, 2H), 6.85 (br. s., 1H), 7.53-7.63 (m, 2H), 7.66 (d, J=8.1 Hz, 2H),7.69 (d, J=2.0 Hz, 1H), 7.76 (d, J=8.1 Hz, 2H), 7.84 (s, 1H); MS m/z496.2 (M+H)⁺.

Following the procedure described in Example 10, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 119

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 1.45- 1.68 (m, 1 H), 1.83-2.13 (m, 9 H), 2.31- 2.51 (m, 1 H),3.00-3.16 (m, 3 H), 3.30- 3.49 (m, 2 H), 3.50-3.62 (m, 1 H), 3.62- 3.77(m, 2 H), 6.85 (s, 1 H), 7.56 (d, J = 8.6 Hz, 1 H), 7.61 (d, J = 8.6 Hz,1 H), 7.65 (d, J = 7.3 Hz, 2 H), 7.69 (s, 1 H), 7.73-7.80 (m, 2 H), 7.84(s, 1 H); MS m/z 524.1 (M + H)⁺ 118

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(1-methyl-1H-pyrazol-3-yl)carbonyl]pyrrolidin-3-yl}methyl)-1,3- diazaspiro[4.4]non-1-en-4-one¹H NMR (400 MHz, CDCl₃) δ ppm 1.42- 1.65 (m, 1 H), 1.79 (s, 2 H),1.83-2.12 (m, 9 H), 2.34-2.39 (m, 1 H), 3.43-3.55 (m, 1 H), 3.61-3.81(m, 3 H), 3.82 (s, 1 H), 3.90 (s, 2 H), 4.00 (dd, J 11.7, 7.1 Hz, 1 H),6.72 (dd, J = 8.6, 2.0 Hz, 1 H), 6.84 (s, 1 H), 7.30 (d, J = 2.0 Hz, 1H), 7.50- 7.62 (m, 2 H), 7.62-7.70 (m, 3 H), 7.70- 7.76 (m, 2 H), 7.82(d, J = 10.5 Hz, 1 H); MS m/z 522.2 (M + H)⁺ 117

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δppm 1.39- 1.51 (m, 1 H), 1.67-1.84 (m, 6 H), 1.88- 2.02 (m, 4 H),2.02-2.12 (m, 4 H), 2.26- 2.39 (m, 1 H), 2.99 (dd, J = 10.4, 7.2 Hz, 1H), 3.20-3.37 (m, 6 H), 3.63-3.78 (m, 2 H), 6.85 (s, 1 H), 7.53-7.63 (m,2 H), 7.63-7.68 (m, 2 H), 7.69 (d, J = 2.0 Hz, 1 H), 7.75 (d, J = 8.3Hz, 2 H), 7.84 (s, 1 H); MS m/z 511.2 (M + H)⁺ 189

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)-1-(pyrrolidin-1-ylsulfonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.51-1.63 (m, 1 H), 1.84-1.90 (m, 4 H), 1.90-2.01(m, 1 H), 2.01-2.16 (m, 4 H), 2.17-2.27 (m, 2 H), 2.28-2.38 (m, 2 H),2.55 (dt, J = 14.0, 7.1 Hz, 1 H), 3.00 (dd, J = 10.0, 6.4 Hz, 1 H),3.18-3.31 (m, 6 H), 3.35 (dd, J = 10.1, 7.0 Hz, 1 H), 3.93 (d, J = 7.3Hz, 2 H), 6.87 (d, J = 1.2 Hz, 1 H), 7.58 (dd, J = 8.6, 1.7 Hz, 1 H),7.63 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.2 Hz, 1 H), 7.84 (d, J = 8.6Hz, m2 H), 7.86-7.91 (m, 3 H) MS m/z 547.2 (M + H)⁺  90

3-{[(3R)-1-Acryloylpyrrolidin-3-yl]methyl}-2-[4-(1-benzofuran-5-yl)phenyl]-8-benzyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 1.40-1.67 (m, 2 H), 1.76-2.02 (m, 2 H), 2.08- 2.24 (m, 2 H), 2.27-2.53 (m, 1H), 2.62- 2.74 (m, 2 H), 2.84-2.94 (m, 2 H), 3.03- 3.16 (m, 1 H),3.27-3.45 (m, 1 H), 3.45- 3.59 (m, 2 H), 3.59-3.77 (m, 4 H), 5.56- 5.70(m, 1 H), 6.19-6.39 (m, 2 H), 6.79- 6.90 (m, 1 H), 7.23-7.30 (m, 1 H),7.34 (t, J = 7.1 Hz, 2 H), 7.37-7.41 (m, 2 H), 7.55 (d, J = 8.6 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1 H), 7.63-7.67 (m, 2 H), 7.69 (d, J = 2.0 Hz,1 H), 7.76 (dd, J = 8.1, 5.1 Hz, 2 H), 7.84 (s, 1 H); MS m/z 573.0 (M +H)⁺

Example 112-(4-(Benzofuran-5-yl)phenyl)-3-(((R)-1-((S)-tetrahydro-furan-2-carbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(Compound #190)

To a stirring solution of(R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one(44 mg, 0.109 mmol) and tetrahydro-furan-2-carboxylic acid (12.9 mg,0.109 mmol) in DCM (2.5 mL) and Et₃N (0.22 mL, 1.63 mmol) was added HATU(53.8 mg, 0.14 mmol). After stirring at room temperature overnight, thereaction mixture was concentrated in vacuo and the resulting residue waspurified by flash chromatography (silica gel, 25% to 65% EtOAc inheptane) to yield2-[4-(1-benzofuran-5-yl)phenyl]-3-({(3R)-1-[(2S)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one(36.7 mg, 66%).

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43-1.70 (m, 1H), 1.81-2.11 (m,9H), 2.11-2.32 (m, 4H), 2.38-2.62 (m, 1H), 3.11 (dd, J=12.2, 7.3 Hz,1H), 3.28-3.44 (m, 1H), 3.49-3.65 (m, 2H), 3.77-3.96 (m, 4H), 4.37-4.47(m, 1H), 6.86 (d, J=2.2 Hz, 1H), 7.56 (dd, J=8.8, 2.0 Hz, 1H), 7.62 (d,J=8.6 Hz, 1H), 7.71 (d, J=2.2 Hz, 1H), 7.80-7.90 (m, 5H);

MS m/z 512.3 (M+H)⁺.

Following the procedure described in Example 11, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 191

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹HNMR (400 MHz, CHLOROFORM-d) δ ppm 1.46-1.71 (m, 1 H), 1.84-2.14 (m, 9H), 2.15-2.32 (m, 4 H), 2.51 (dt, J = 14.7, 7.1 Hz, 1 H), 3.09-3.21 (m,1 H), 3.42 (dt, J = 11.1, 7.6 Hz, 1 H), 3.52-3.63 (m, 1 H), 3.63-3.77(m, 1 H), 3.79-3.86 (m, 1 H), 3.86-3.97 (m, 3 H), 4.34-4.47 (m, 1 H),6.86 (d, J = 1.2 Hz, 1 H), 7.56 (d, J = 8.6 Hz, 1 H), 7.59-7.64 (m, 1H), 7.68- 7.73 (m, 1 H), 7.81-7.91 (m, 5 H); MS m/z 512.3 (M + H)⁺ 192

1-{[(3R)-3-({2-[4-(1-Benzofuran-5-yl)phenyl]-4-oxo-1,3-diazaspiro[4.4]non-1- en-3-yl}methyl)pyrrolidin-1-yl]carbonyl}cyclopropancarbonitrile ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm1.42-1.63 (m, 3 H), 1.63-1.81 (m, 2 H), 1.99-2.16 (m, 5 H), 2.18-2.29(m, 2 H), 2.29-2.41 (m, 2 H), 2.47-2.68 (m, 1 H), 3.16 (dd, J = 12.3,7.2 Hz, 1 H), 3.39- 3.67 (m, 2 H), 3.82 (dt, J = 10.6, 7.5 Hz, 1 H),3.89-4.06 (m, 3 H), 6.87 (d, J = 1.7 Hz, 1 H), 7.58 (dd, J = 8.6, 1.7Hz, 1 H), 7.64 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.2 Hz, 1 H),7.81-7.94 (m, 5 H); MS m/z 507.1 (M + H)⁺

Example 128-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #160)

and8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #161)

STEP A:(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,and(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

10% Palladium on carbon (0.10 g) was added to a solution of8-benzyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.635 g, 1.06 mmol) in MeOH (15 mL) under a nitrogen atmosphere. Thereaction vessel was connected to a balloon filled with hydrogen and thevessel was evacuated and filled with hydrogen three times. Afterstirring under hydrogen overnight, HOAc (1 mL, 15.8 mmol) was added andthe reaction again placed under hydrogen atmosphere and stirred forseveral days. The suspension was filtered through a pad of diatomaceousearth and the solids were washed three times with MeOH (20 mL). Thecombined filtrates were concentrated to dryness, then dissolved in DCM(30 mL) and washed with 1M aqueous NaOH (20 mL). The organic layer wasdried over MgSO₄, filtered, and concentrated to yield a mixture of(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-oneand(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.506 g).

MS n/z 512 and 514 (M+H)⁺.

STEP B:8-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #160), and8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #161)

Acetyl chloride (0.283 mL, 3.98 mmol) was added to the mixture of(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,and(R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,prepared as described in Step A above, (0.406 g, 0.793 mmol) and Et₃N(1.12 mL, 8.00 mmol) in DCM (20 mL) at 0° C. The resulting mixture wasallowed to warm to room temperature and MeOH (2 mL) was added after 30min. DCM (20 mL) was added and the organic solution was washed once with1M aq. NaOH. The organic layer was dried over MgSO₄, filtered, andconcentrated; the resulting residue was filtered through a short pad ofsilica gel and eluted with 10% MeOH/DCM. Fractions containing thedesired products were concentrated to yield a mixture that was furtherpurified by reverse-phase HPLC using 10-46% CH₃CN/0.1% aq. TFA.Fractions containing a mixture of the desired products were combined,diluted with DCM (50 mL), and washed with 1 M aq. NaOH. The organiclayer was dried over MgSO₄, filtered, and concentrated. The resultingmaterial was re-purified by flash chromatography (silica gel, 0-10%MeOH/DCM) to yield

(a)8-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.030 g).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.81 (m, 2H), 0.85-1.01 (m, 2H),1.35-1.73 (m, 3H), 1.72-2.10 (m, 4H), 2.13-2.17 (m, 3H), 2.20 (d, J=2.2Hz, 3H), 2.23-2.56 (m, 2H), 2.82-4.01 (m, 12H), 4.35-4.60 (m, 1H), 4.68(s, 1H), 4.79 (s, 1H), 7.19-7.35 (m, 1H), 7.35-7.57 (nm, 2H), 7.56-7.84(m, 4H); MS m/z 596, m.p. 104.5° C.

(b)8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.010 g).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.67-0.80 (m, 2H), 0.96 (d, J=3.8 Hz, 2H),1.37-1.68 (m, 4H), 1.78-2.08 (m, 3H), 2.12 (s, 3H), 2.21 (d, J=2.1 Hz,3H), 2.23-2.75 (m, 2H), 2.76-3.11 (m, 4H), 3.11-3.94 (m, 9H), 4.21-4.55(m, 1H), 4.68 (s, 1H), 4.79 (s, 1H), 5.36-5.56 (m, 1H), 7.16-7.28 (m,1H), 7.34-7.49 (m, 4H), 7.66 (d, J=6.7 Hz, 2H); MS m/z 598.

and (c) a mixture of the compound of (a) and the compound of (b); (0.120g).

Example 133-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-yl)phenyl)-8-(1-methylethy)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(Compound #163)

A mixture of3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one(0.080 g, 0.158 mmol), acetone (0.0464 mL, 0.632 mmol), sodiumtriacetoxyborohydride (0.0403 g, 0.190 mmol), and AcOH (0.010 mL, 0.158mmol) in THF (5 mL) was stirred at room temperature for 24 h. 1M aq.NaOH (5 mL) was added and the reaction mixture was extracted with DCM(2×10 mL). The combined organic layers were dried over MgSO₄, filtered,and concentrated. The resulting residue was purified by flashchromatography (silica gel, 0-10% of MeOH in DCM). Fractions containingdesired product were concentrated and re-purified by reverse-phase HPLCusing 30-73% 1:1 CH₃CN/MeOH in aq. 25 mM NH₄CO₃. Fractions containingdesired product were concentrated, dissolved in MeOH (2 mL), and treatedwith 4N HCl in 1,4-dioxane (0.100 mL). The resulting solution wasconcentrated and the residue triturated with Et₂O, filtered, and driedunder high vacuum to yield3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one,dihydrochloride, as a white solid, (0.069 g, 70%).

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=3.6 Hz, 4H), 1.27-1.40 (m,7H), 1.47-2.04 (m, 5H), 2.14-2.43 (m, 1H), 2.86 (dd, J=11.7, 7.3 Hz,0.5H), 3.03-3.20 (m, 1H), 3.20-3.34 (m, 2.5H), 3.43-3.63 (m, 7H), 3.69(t, J=7.3 Hz, 2H), 7.99 (dd, J=7.9, 5.2 Hz, 2H), 8.20 (dd, J=8.0, 3.8Hz, 2H), 8.47 (d, J=8.8 Hz, 1H), 8.55 (d, J=6.5 Hz, 1H), 8.68 (d, J=8.7Hz, 1H), 8.73 (d, J=6.6 Hz, 1H), 8.79 (s, 1H), 9.95 (s, 1H), 10.74-11.18(m, 1H); MS m/z 550; m.p.>300° C.

Following the procedure described in Example 13, above, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art, the following compoundsof formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 162

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(1-methylethyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-onedihydrochloride MS m/z 553 (M + H)⁺ 166

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(1-methylethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MSm/z 525 (M + H)⁺ 167

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.76(m, 2 H), 0.88-0.97 (m, 2 H), 1.14 (d, J = 6.5 Hz, 6 H), 1.36-1.74 (m, 4H), 1.74-2.09 (m, 2 H), 2.06-2.56 (m, 4 H), 2.75-3.08 (m, 5 H),3.12-3.36 (m, 1 H), 3.48-3.80 (m, 3 H), 6.85 (d, J = 1.8 Hz, 1 H),7.51-7.57 (m, 1 H), 7.58-7.71 (m, 4 H), 7.71-7.80 (m, 2 H), 7.80-7.88(m, 1 H); MS m/z 539 (M + H)⁺ 169

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(1-methylethyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one MSm/z 539 (M + H)⁺ m.p. 93.1° C. 184

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.56-0.69 (m, 4 H), 0.96-1.09 (m, 6 H), 1.41-1.94 (m, 6H), 2.09-2.34 (m, 1 H), 2.34-2.39 (m, 3 H), 2.37 (s, 3 H), 2.50 (s, 3H), 2.56-2.70 (m, 2 H), 2.70-2.91 (m, 2 H), 3.04-3.17 (m, 1 H), 3.26 (d,J = 4.9 Hz, 1 H), 3.33-3.59 (m, 1 H), 3.65 (t, J = 7.5 Hz, 2 H), 7.67(dd, J = 9.2 Hz, 1 H), 7.78 (dd, J = 7.8, 5.6 Hz, 2 H), 7.91-8.03 (m, 4H); MS m/z 583 (M + H)⁺ m.p. 118.4° C. 186

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2-methyl-1-benzofuran-5-yl)phenyl]-8-(1-methylethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 4.5 Hz, 4 H), 1.16-2.06 (m, 13H), 2.07-2.45 (m, 4 H), 2.76-3.27 (m, 4 H), 3.40-3.76 (m, 7 H), 6.66 (s,1 H), 7.60 (s, 2 H), 7.72-7.84 (m, 2 H), 7.84- 7.97 (m, 3 H); MS m/z 553(M + H)⁺ m.p. 143.1° C. 187

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz,CDCl₃) δ ppm 0.69 (dd, J = 7.8, 3.2 Hz, 2 H), 0.84-0.94 (m, 2 H), 1.14(d, J = 6.6 Hz, 6 H), 1.20-1.36 (m, 2 H), 1.64 (d, J = 12.8 Hz, 2 H),1.98- 2.26 (m, 3 H), 2.63-3.05 (m, 5 H), 3.49- 3.63 (m, 1 H), 3.77-4.02(m, 3 H), 4.09- 4.24 (m, 1 H), 6.63 (br. s., 1 H), 7.27- 7.33 (m, 1 H),7.42-7.52 (m, 2 H), 7.61 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2H), 7.90 (s, 1 H), 8.55 (br. s., 1 H); MS m/z 524 (M + H)⁺ 188

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.55-0.67 (m, 4 H), 1.02 (d, J = 6.3 Hz, 6 H), 1.23 (br.s., 1 H), 1.31-1.57 (m, 3 H), 1.85 (t, J = 9.9 Hz, 2 H), 2.54-2.70 (m, 3H), 2.70-2.89 (m, 3 H), 3.65-3.81 (m, 2 H), 3.86 (d, J = 7.1 Hz, 2 H),4.14 (t, J = 7.9 Hz, 1 H), 7.58-7.70 (m, 1 H), 7.75 (d, J = 8.0 Hz, 3H), 7.90 (d, J = 8.0 Hz, 2 H), 8.16 (d, J = 4.7 Hz, 2 H), 13.17 (br. s.,1 H); MS m/z 525 (M + H)⁺ m.p. 162.6° C.

Example 145-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one(Compound #49)

STEP A: tert-Butyl3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate

To a stirring solution of5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (9.9 g, 33.6 mmol)and tert-butyl 3-(bromomethyl)azetidine-1-carboxylate (12.6 g, 50.4mmol) in DMF (180 mL) was added Cs₂CO₃ (36.5 g, 67.1 mmol). Afterstirring for 3 h at 830° C. under nitrogen, the reaction mixture wascooled and filtered through a pad of diatomaceous earth. The filtratewas concentrated and the residue was partitioned between EtOAc (250 mL)and water (150 mL). The organic phase was washed with brine, dried overMgSO₄, filtered, and concentrated in vacuo. The residue was purified byflash chromatography (silica gel, 0-75% EtOAc in heptane) to yieldtert-butyl3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate(10.7 g, 73%); MS m/z 434 (M+H)⁺.

STEP B:6-(Azetidin-3-ylmethyl)-5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

TFA (50 mL) was added to an ice-cold solution of tert-butyl3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate(10.7 g, 24.6 mmol) in DCM (100 mL). The solution was allowed to warm toroom temperature and was stirred 1 h. The solution was concentrated invacuo and the residue was co-evaporated twice with toluene (100 mL). Theresidue was pumped at high vacuum to yield6-(azetidin-3-ylmethyl)-5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-oneTFA salt (20.3 g), which was used in the next step without purification;MS m/z 334 (M+H)⁺.

STEP C:5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl-4,6-diazaspiro[2.4]hept-4-en-7-one

Cyclopropanecarbonyl chloride (2.46 mL, 27.1 mmol) was added dropwise toan ice cold solution of5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(13.9 g, 24.6 mmol) and TEA (7.0 mL, 50.2 mmol) in DCM (100 mL). Theresulting mixture was stirred 1 h and MeOH (2 mL) was added. Thereaction mixture was diluted with DCM (150 mL) and washed successivelywith water (150 mL) and 1M aqueous Na₂CO₃ (150 mL). The organic layerwas dried over MgSO₄ and concentrated in vacuo to yield a residue, whichwas purified by flash chromatography (silica gel, 0-5% MeOH in DCM) togive5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-oneas an amorphous solid (7.66 g, 77%); MS m/z 402 (M+H)⁺.

STEP D:5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one(Compound #49)

To a solution of5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one(7.66 g, 19.0 mmol) in acetonitrile (100 mL) was added2-(benzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.58 g,22.9 mmol), aqueous 1.0M Na₂CO₃ (40 mL, 40 mmol) andbis(triphenylphosphine)palladium(II) chloride (0.33 g, 0.48 mmol). Thereaction mixture was bubbled with nitrogen for 5 min and heated at 85°C. for 2 h under nitrogen atmosphere. The resulting mixture was cooledto room temperature and partitioned between EtOAc (200 mL) and brine (50mL). The aqueous layer was extracted with EtOAc (50 mL) and the combinedorganic layers were dried over MgSO₄ and concentrated in vacuo to yielda reddish oil. The reddish oil was purified by flash chromatography(silica gel, 0-5% MeOH in DCM) to yield a beige foam after concentrationand pumping at high vacuum. The foam was crystallized from acetonitrile(30 mL) and washed with acetonitrile (3×10 mL) to yield5-[4-(1-benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-oneas a light beige solid (5.70 g, 68%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.76 (m, 2H), 0.86-0.97 (m, 2H),1.22-1.36 (m, 1H), 1.74-1.83 (m, 2H), 1.83-1.94 (m, 2H), 2.77-2.95 (m,1H), 3.62 (dd, J=9.7, 5.6 Hz, 1H), 3.90-4.16 (m, 4H), 4.23 (t, J=8.2 Hz,1H), 6.85 (d, J=2.1 Hz, 1H), 7.53-7.74 (m, 5H), 7.78 (d, J=8.4 Hz, 2H),7.84-7.89 (m, 1H); MS m/z 440 (M+H)⁺; m.p. 181.3° C.

An additional batch of the compound of Example 14 was prepared, withmeasured physical properties as listed below.

ID No. Structure Compound Name & Physical Data 49

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyly-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.76 (m, 2 H), 0.86-0.97 (m, 2 H), 1.22- 1.36 (m, 1 H), 1.74-1.83 (m, 2H), 1.83- 1.94 (m, 2 H), 2.77-2.95 (m, 1 H), 3.62 (dd, J = 9.7, 5.6 Hz,1 H), 6.85 (d, J = 2.1 Hz, 1 H), 7.53-7.74 (m, 5 H), 7.78 (d, J = 8.4Hz, 2 H), 7.84-7.89 (m, 1 H); MS m/z 440 (M + H)⁺ m.p. 182.0° C.

Additional representative compounds of formula (I) of the presentinvention were prepared according to the procedures as described in thegeneral synthesis schemes and examples detailed herein, selecting andsubstituting the appropriate reagents, starting materials, andpurification methods, and adjusting reaction temperatures, times andother variables or parameters, as needed or desirable, as would bereadily recognized by those skilled in the art. Measured physicalproperties for said compounds were as listed below.

ID No. Structure Compound Name & Physical Data  44

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-{4-[6-(4-methylpiperazin-1- yl)pyridin-3-yl]phenyl}-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 541.3 (M + H)⁺  95

2-[(3R)-3-({2-[4-(1-Benzofuran-5- yl)phenyl]-8-benzyl-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3- yl}methyl)pyrrolidin-1-yl]acetamide MS m/z576.0 (M + H)+  96

2-[4-(1-Benzofuran-5-yl)phenyl]-8-benzyl- 3-{[(3R)-1-(2-cyclopropyl-2-oxoethyl)pyrrolidin-3-yl]methyl}-1,3,8- triazaspiro[4.5]dec-1-en-4-oneMS m/z 600.9 (M + H)+ 200

(R)-6- hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.84-0.94 (m, 2 H), 1.09 (d, J = 9.6 Hz, 1 H), 1.22(br. s., 1 H), 1.49 (d, J = 11.1 Hz, 1 H), 1.75-1.80 (m, 2 H), 1.84-1.98(m, 3 H), 2.45 (dt, J = 14.1, 7.1 Hz, 1 H), 2.87 (br. s., 0.5 H), 3.09(br. s., 1 H), 3.38 (br. s., 0.5 H), 3.52 (br. s., 1.5 H), 3.64 (br. s.,0.5 H), 3.80 (d, J = 6.6 Hz, 3 H), 4.09-4.15 (m, 3 H), 7.50 (d, H = 9.1Hz, 1 H), 7.68 (d, J = 7.6 Hz, 3 H), 7.78 (d, J = 8.6 Hz, 2 H), 7.98 (s,1 H), 8.06 (s, 1 H), MS m/z 484.1 (M + H)+ 201

(R)-5-(4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.44-0.55 (m, 2 H), 0.78-0.86 (m, 1 H), 0.91 (d, J =9.1 Hz, 1 H), 1.22 (s, 3 H), 1.60 (br. s., 1 H), 1.68 (br. s., 1 H),1.74-1.81 (m, 2 H), 1.84-1.98 (m, 3 H), 2.46 (dt, J = 14.4, 7.5 Hz, 1H), 3.09 (br. s., 1 H), 3.34 (br. s., 0.5 H), 3.48 (br. s., 1.5 H), 3.65(br. s., 1 H), 3.82 (br. s., 2 H), 4.13 (s, 3 H), 7.50 (d, J = 8.6 Hz, 1H), 7.68 (d, J = 7.6 Hz, 3 H), 7.75-7.81 (m, 2 H), 7.97 (s, 1 H), 8.06(s, 1 H). MS m/z 482.2 (M + H)⁺ 202

(R)-5-(4′-chloro-2′-fluoro[1,1′-biphenyl]-4- yl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.92 (br. s., 2 H), 1.12 (br. s., 2 H), 1.73-1.81(m, 2 H), 1.83-1.98 (m, m3 H), 2.44 (dt, J = 14.1, 7.1 Hz, 1 H), 2.60(d, J = 18.2 Hz, 1 H), 2.69 (br s, 1 H), 2.74 (br. s., 1 H), 2.99 (d, J= 13.1 Hz, 1 H), 3.10 (d, J = 14.7 Hz, 1 H), 3.39 (br. s., 1 H), 3.52(br. s., 1 H), 3.65 (br. s., 1 H), 3.79 (d, J = 7.1 Hz, 3 H), 7.19-7.26(m, 3 H), 7.41 (q, J = 8.6 Hz, 2 H), 7.61 (d, J = 7.1 Hz, 1 H), 7.89 (d,J = 8.6 Hz, 1 H). MS m/z 482.2 (M + H)+ 203

(R)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(6-methoxynaphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.88 (br. s., 2 H), 1.07 (br. s., 2 H), 1.49 (br.s., 1 H), 1.74-1.80 (m, 2 H), 1.84-1.97 (m, 3 H), 2.44 (dt, J = 14.0,6.9 Hz, 1 H), 3.10 (br. s., 1 H), 3.32 (br. s., 1 H), 3.51 (br. s., 1.5H), 3.59-3.72 (m, 1 H), 3.80 (d, J = 6.6 Hz, 2.5 H), 3.95 (s, 3 H),7.15-7.23 (m, 2 H), 7.69 (d, J = 8.6 Hz, 2 H), 7.74 (d, J = 8.6 Hz, 1H), 7.79- 7.87 (m, 4 H), 8.03 (s, 1 H). MS m/z 510.4 (M + H)+ 204

5-(4-(1-methyl-1H-indazol-5-yl)phenyl)-6-(((3R)-1-(oxetane-2-carbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.44-1.57 (m, 1 H), 1.73-1.81 (m, 2 H), 1.87 (d, J =3.0 Hz, 2 H), 1.90-1.99 (m, 1 H), 2.46 (dt, J = 13.6, 6.8 Hz, 1 H),2.68-2.84 (m, 1 H), 2.86-3.04 (m, 1 H), 3.05-3.23 (m, 1 H), 3.24-3.33(m, 0.5 H), 3.33-3.45 (m, 1 H), 3.46-3.66 (m, 1.5 H), 3.74-3.87 (m, 2H), 4.13 (s, 3 H), 4.48-4.59 (m, 1 H), 4.59-4.70 (m, 1 H), 5.04-5.21 (m,1 H), 7.50 (d, J = 8.6 Hz, 1 H), 7.64-7.72 (m, 3 H), 7.77 (d, J = 8.6Hz, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H). MS m/z 494.4 (M + H)+ 205

5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-6-((1-(tetrahytdro-furan-2-carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 1.55-1.64 (m, 2 H), 1.64-1.83 (m, 5 H),1.86-1.99 (m, 1 H), 2.36 (s, 3 H), 2.56- 2.66 (m, 1 H), 3.36-3.44 (m, 1H), 3.59- 3.74 (m, 5 H), 3.74-3.84 (m, 1 H), 4.10 (s, 3 H), 4.11-4.23(m, 2 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.67-7.87 (m, 4 H), 8.13 (d, J =2.9 Hz, 2 H). MS m/z 498.3 (M + H)+ 206

(S)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-6-((1-(tetrahydro-furan-2-carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 1.56-1.64 (m, 2 H), 1.64-1.85 (m, 5 H),1.86-1.99 (m, 1 H), 2.36 (s, 3 H), 2.61 (d, J = 4.9 Hz, 1 H), 3.35-3.44(m, 1 H), 3.59-3.74 (m, 5 H), 3.74-3.85 (m, 1 H), 4.10 (s, 3 H),4.12-4.23 (m, 2 H), 7.55 (d, J = 8.0 Hz, 1 H), 87.68-7.85 (m, 4 H),8.11-8.17 (m, 2 H). MS m/z 498.2 (M + H)+ 207

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.11 (d, J = 2.2 Hz, 2 H), 0.51 (s, 2 H), 0.83 (s, 3 H), 1.29-1.40(m, 2 H), 1.48- 1.58 (m, 2 H), 2.12 (s, 3 H), 2.29-2.42 (m, 1 H),3.13-3.39 (m, 2 H), 3.39-3.50 (m, 2 H), 3.55-3.75 (m, 2 H), 3.85 (s, 3H), 7.31 (d, J = 8.0 Hz, 1 H), 7.43-7.62 (m, 4 H), 7.88 (s, 2 H). MS m/z482.3 (M + H)+ 208

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-methylcyclobutanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 1.14 (s, 3 H), 1.45-1.63 (m, 5 H), 1.71- 1.89 (m, 3 H), 2.02-2.29(m, 2 H), 2.36 (s, 3 H), 2.58 (br. s., 1 H), 3.34-3.47 (m, 2 H),3.53-3.67 (m, 1 H), 3.75 (d, J = 15.1 Hz, 2 H), 4.00 (t, J = 8.4 Hz, 1H), 4.10 (s, 3 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.67-7.84 (m, 4 H), 8.13(s, 2 H). MS m/z 496.3 (M + H)+ 209

(R)-5-(3-chloro-4-fluoro-[1,1-biphenyl]-4- yl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.65 (d, J = 6.7 Hz, 4 H), 1.33-1.66 (m, 4 H), 1.69-1.93 (m, 3 H),2.25 (d, J = 7.0 Hz, 1 H), 2.88 (dd, J = 11.8, 6.9 Hz, 1 H), 3.09-3.19(m, 1 H), 3.19-3.30 (m, 1 H), 3.40-3.62 (m, 1 H), 3.75 (t, J = 6.4 Hz, 2H), 7.56 (t, J = 8.9 Hz, 1 H), 7.81 (dd, J = 8.3, 4.2 Hz, 3 H), 7.90(dd, J = 8.4, 2.2 Hz, 2 H), 8.01 (d, J = 7.0 Hz, 1 H). MS m/z 466 (M +H)+ 210

(S)-5-(4-(1H-indol-5-yl)phenyl)-6-((1-(cy7clopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.55-0.75 (m, 4 H), 1.35-1.69 (m, 4 H), 1.69-1.97 (m, 3 H),2.20-2.35 (m, 1 H), 2.92 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06- 3.21 (m, 1H), 3.21-3.31 (m, 1 H), 3.42- 3.66 (m, 1.5 H), 3.77 (t, J = 6.7 Hz, 2H), 6.52 (d, J = 2.9 Hz, 1 H), 7.41 (d, J = 3.0 Hz, 1 H), 7.44-7.55 (m,2 H), 7.77 (dd, J = 8.2, 3.7 Hz, 2 H), 7.86 (d, J = 89.1 Hz, 2 H), 7.94(s, 1 H), 11.09 (br. s., 1 H). MS m/z 453 (M + H)+ 211

(S)-5-(4-(benzo[b]thiophen-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.32-0.50 (m, 4 H), 1.11-1.44 (m, 4 H), 1.46-1.72 (m, 3 H),1.97-2.12 (m, 1 H), 2.67 (dd, J = 11.8, 6.9 Hz, 10.5 H), 2.84- 2.98 (m,1 H), 2.98-3.07 (m, 1 H), 3.18- 3.40 (m, 1.5 H), 3.54 (t, mJ = 6.5 Hz, 2H), 7.32 (d, J = 5.5 Hz, 1 H), 7.47-7.65 (m, 4 H), 7.65-7.76 (m, 2 H),7.90 (d, J = 8.5 Hz, 1 H), 8.05 (s, 1 H). MS m/z 470 (M + H)+ 212

(R)-2-(5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-1H-indole-3-yl)acetonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 6.7 Hz, 4H), 1.52-1.69 (m, 4 H), 1.70-1.97 (m, 3 H), 2.29 (br. s., 0.5 H), 2.38(br. s., 0.5 H), 2.84-3.00 (m, 0.5 H), 3.19 (br. s., 1 H), 3.41 (br. s.,0.5 H), 3.45-3.66 (m, 2 H), 3.78 (t, J = 7.1 Hz, 2 H), 4.13 (s, 2 H),7.43 (s, 1 H), 7.47-7.61 (m, 2 H), 7.73-7.85 (m, 2 H), 7.85-7.95 (m, 2H), 8.02 (s, 1 H), 11.26 (br. s., 1 H). MS m/z 492 (M + H)+ 213

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2,3-dimethyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.66 (br. s., 4 H), 1.60 (br. s., 4 H), 1.79 (br. s., 3 H), 2.23(s, 3 H), 2.35 (br. s., 3 H), 2.37-2.47 (m, 1 H), 2.93 (br. s., 0.5 H),3.16 (br. s., 1 H), 3.28 (br. s., 1 H), 3.50 (br. s., 1.5 H), 3.78 (br.s., 2 H), 7.28- 7.47 (m, 2 H), 7.75 (br. s., 3 H), 7.87 (d, J = 7.3 Hz,2 H), 10.79 (br. s., 1 H). MS m/z 481 (M + H)+ 214

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.52-0.78 (m, 4 H), 1.60 (br. s., 4 H), 1.78 (br. s., 3 H), 2.29(br. s., 1 H), 2.42 (s, 3 H), 2.92 (br. s., 0.5 H), 3.07-3.21 (m, 1 H),3.27 (br. s., 1 H), 3.48 (br. s., 1.5 H), 3.78 (br. s., 2 H), 6.22 (br.s., 1 H), 7.39 (br. s., 2 H), 6.22 (br. s., 1 H), 7.39 (br. s., 2 H),7.83 (s, 3 H), 7.79 (s, 2 H), 11.04 (br. s., 1 H). MS m/z 467 (M + H)+215

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.64 (d, J = 5.8 Hz, 4 H), 1.43 (d, J = 19.0 Hz, 1 H), 1.50-1.69(m, 3 H), 1.79 (d, J = 3.8 Hz, 2 H), 1.88 (d, J = 6.3 Hz, 1 H), 2.29(br. s., 1 H), 2.92 (d, J = 4.8 Hz, 0.5 H), 3.08-3.21 (m, 1 H),3.21-3.31 (m, 1 H), 3.44-3.58 (m, 1.5 H), 3.78 (t, J = 6.7 Hz, 2 H),3.84 (s, 3 H), 6.52 (d, J = 2.6 Hz, 1 H), 7.39 (d, J = 2.7 Hz, 1 H),7.57 (s, 2 H), 7.72-7.82 (m, 2 H), 7.82-7.91 (m, 2 H), 7.95 (s, 1 H). MSm/z 467 (M + H)+ 216

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-(hydroxymethyl)-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-enn-7-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.67 (d, J = 5.8 Hz, 4 H), 1.46 (dd, J = 12.5, 7.3 Hz, 1H), 1.57-1.72 (m, 3 H), 1.73- 1.84 (m, 2 H), 1.84-1.98 (m, 1 H), 2.31(t, J = 7.0 Hz, 0.5 H), 2.43 (d, J = 13.7 Hz, 0.5 H), 2.83-3.00 (m, 0.5H), 3.09-3.23 (m, 1 H), 3.24-3.34 (m, 1 H), 3.40-3.59 (m, 1.5 H),3.74-3.91 (m, 2 H), 4.67 (d, J = 5.5 Hz, 2 H), 5.32 (t, J = 5.6 Hz, 1H), 6.40 (s, 1 H), 7.43-7.52 (m, 2 H), 7.74- 7.84 (m, 2 H), 7.88 (d, J =7.7 Hz, 3 H), 11.18 (s, 1 H). MS m/z 483 (M + H)+ 217

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(3-(2-hydroxyethyl)-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.51-0.75 (m, 4 H), 1.35-1.54 (m, 1 H), 1.54-1.68 (m, 3H), 1.70-1.81 (m, 2 H), 1.81-1.96 (m, 1 H), 2.22-2.47 (m, 1 H),2.85-3.01 (m, 2.5 H), 3.08-3.22 (m, 1 H), 3.22-3.32 (m, 1 H), 3.41-3.63(m, 1.5 H), 3.65-3.74 (m, 2 H), 3.78 (t, J = 7.2 Hz, 2 H), 4.64 (t, J =5.4 Hz, 1 H), 7.15- 7.28 (m, 1 H), 7.39-7.53 (m, 2 H), 7.72- 7.82 (m, 2H), 7.82-7.97 (m, 3 H), 10.93 (s, 1 H). MS m/z 497 (M + H)+ 218

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(1,3-dimethyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.72 (dd, J = 7.7, 3.0 Hz, 2 H), 0.87- 1.03 (m, 2H), 1.46-1.58 (m, 1 H), 1.68- 1.75 (m, 1 H), 1.75-1.83 (m, 2 H), 1.84-1.92 (m, 2 H), 2.02 (d, J = 6.0 Hz, 1 H), 2.37-2.52 (m, 1 H), 2.65 (s, 3H), 3.07 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.23-3.40 (m, 1 H), 3.48-3.75(m, 2.5 H), 3.75- 3.93 (m, 2 H), 4.06 (s, 3 H), 7.44 (d, J = 8.7 Hz, 1H), 7.64-7.74 (m, 3 H), 7.76- 7.85 (m, 2 H), 7.90 (s, 1 H). MS m/z 482(M + H)+ 219

(R)-5-(4-(3-aminoisoquinolin-6-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.66-0.80 (m, 2 H), 0.88-1.05 (m, 2 H), 1.41-1.60(m, 2 H), 1.60-1.85 (m, 2 H), 1.85-1.94 (m, 2 H), 1.94-2.10 (m, 1 H),2.36-2.52 (m, 0.5 H), 2.52-2.68 (m, 0.5 H), 3.07 (dd, J = 12.0, 7.1 Hz,0.5 H), 3.21-3.42 (m, 1 H), 3.51-3.73 (m, 2.5 H), 3.75-3.94 (m, 2 H),4.55 (br. s., 2 H), 6.81 (s, 1 H), 7.53 (d, J = 8.5 Hz, 1 H), 7.67-7.81(m, 3 H), 7.81-7.96 (m, 3 H), 8.92 (s, 1 H). MS m/z 480 (M + H)+ 220

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(3-fluoroisoquinolin-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.90-1.04 (m, 2 H), 1.52 (qd, J= 8.2, 4.2 Hz, 1 H), 1.77- 1.85 (m, 3 H), 1.85-1.93 (m, 2 H), 1.93- 2.10(m, 1 H), 2.44 (dt, J = 14.3, 7.2 Hz, 1 H), 3.05 (dd, J = 12.0, 7.2 Hz,0.5 H), 3.23- 3.41 (m, 1 H), 3.43-3.62 (m, 2 H), 3.62- 3.82 (m, 1.5 H),3.82-3.90 (m, 1 H), 7.33 (s, 1 H), 7.73-7.81 (m, 2 H), 7.81- 7.93 (m, 3H), 8.05 (s, 1 H), 8.12 (d, J = 8.7 Hz, 1 H), 9.02 (s, 1 H). MS m/z 483(M + H)+ 221

(R)-6-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-1-methyl-1H-indazole- 3-carboxamide ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.65-0.81 (m, 2 H), 0.87-1.06 (m, 2 H), 1.46-1.58(m, 1 H), 1.66 (d, J = 7.6 Hz, 1 H), 1.75-1.84 (m, 2 H), 1.84-1.93 (m, 2H), 2.01 (d, J = 12.0 Hz, 1 H), 2.44 (br. s., 1 H), 3.07 (dd, J = 11.9,7.1 Hz, 0.5 H), 3.22-3.41 (m, 1 H), 3.49-3.68 (m, 2.5 H), 3.75-3.95 (m,2 H), 4.17 (s, 3 H), 5.55 (br. s., 1 H), 6.92 (br. s., 1 H), 7.54 (d, J= 8.8 Hz, 1 H), 7.66-7.80 (m, 3 H), 7.85 (dd, J = 8.0, 4.9 Hz, 2 H),8.65 (s, 1 H). MS m/z 511 (M + H)+ 222

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthanitrile ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.66-0.76 (m, 2 H), 0.91 (t, J = 3.8 Hz, 2 H), 1.31(dq, J = 8.3, 4.0 Hz, 1 H), 1.77-1.87 (m, 2 H), 1.88-1.97 (m, 2 H),2.80-2.98 (m, 1 H), 3.56 (dd, J = 9.8, 5.6 Hz, 1 H), 3.75-3.88 (m, 1 H),3.98 (q, J = 9.3 Hz, 3 H), 4.28 (t, J = 8.3 Hz, 1 H), 7.61 (d, J = 11.0Hz, 1 H), 7.67-7.75 (m, 3 H), 7.85-7.93 (m, 1 H), 7.98-8.09 (m, 2 H),8.15 (s, 1 H), 8.31 (s, 1 H). MS m/z 493 (M + H)+ 223

5-(4-(6-fluoronaphthalen-2-yl)-2- methylphenyl)-6-((1-(oxetan-2-carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 1.70 (d, J = 4.9 Hz, 4 H), 1.79 (br.s., 2 H), 2.35 (s, 3 H), 2.58-2.72 (m, 1 H), 2.79 (d, J = 15.1 Hz, 1 H),3.38-3.50 (m, 1 H), 3.50-3.81 (m, 3 H), 3.82-4.07 (m, 1.5 H), 4.09-4.32(m, 1 H), 4.37-4.63 (m, 1 H), 4.95-5.12 (m, 0.5 H), 7.20- 7.30 (m, 1 H),7.36 (d, J = 7.6 Hz, 1 H), 7.39-7.48 (m, 1 H), 7.55-7.65 (m, 2 H),7.67-7.77 (m, 1 H), 7.77-7.90 (m, 2 H), 8.00 (s, 1 H). MS m/z 498.2 (M +H)+ 224

6-(3-methyl-4-(6-((1-(oxetane-2-carbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2- naphthonitrile ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 1.80 (d, J = 6.3 Hz, 3 H), 1.85-1.93 (m, 2 H), 2.46(s, 3 H), 2.68-2.81 (m, 1 H), 2.87 (d, J = 4.0 Hz, 1 H), 3.59-3.90 (m, 4H), 3.91-4.16 (m, 2 H), 4.19-4.42 (m, 1 H), 4.47-4.71 (m, 1.5 H), 5.06-5.18 (m, 0.5 H), 7.48 (d, J = 7.7 Hz, 1 H), 7.65-7.75 (m, 3 H),7.85-7.95 (m, 1 H), 8.02 (dd, J = 8.4, 3.4 Hz, 2 H), 8.14 (s, 1 H), 8.30(s, 1 H). MS m/z 505 (M + H)+ 225

6-(3-fluoro-4-(6-((1-(1- fluorocyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm1.08-1.21 (m, 2 H), 1.30 (d, J = 8.9 Hz, 2 H), 1.78-1.88 (m, 2 H),1.88-1.97 (m, 2 H), 2.89-3.01 (m, 1 H), 3.66 (d, J = 4.5 Hz, 1 H),3.81-4.00 (m, 2 H), 4.09 (d, J = 9.3 Hz, 2 H), 4.45 (br. s., 1 H), 7.62(d, J = 10.9 Hz, 1 H), 7.66-7.77 (m, 3 H), 7.85-7.94 (m, 1 H), 8.05 (t,J = 7.8 Hz, 2 H), 8.16 (s, 1 H), 8.32 (s, 1 H). MS m/z 511.2 (M + H)+226

6-(3-fluoro-4-(6-((1-(oxetane-2-carbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2..4]hept-4-en-5-yl)phenyl)-2- naphthonitrile ¹H NMR (300MHz, CHLOROFORM-d) δ ppm 1.73-1.85 (m, 2 H), 1.89 (br. s., 2 H),2.67-3.00 (m, 3 H), 3.59-3.70 (m, 1 H), 3.73-3.96 (m, 2.5 H), 3.99-4.11(m, 1.5 H), 4.25 (t, J = 8.9 Hz, 1 H), 4.45-4.69 (m, 2 H), 5.05-5.16 (m,1 H), 7.54-7.63 (m, 1 H), 7.65-7.73 (m, 3 H), 7.83-7.91 (m, 1 H),7.97-8.08 (m, 2 H), 8.13 (s, 1 H), 8.29 (s, 1 H). MS m/z 509.3 (M + H)+227

6-((1-(cyclopropanec arbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-2H- indazol-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.61-0.74 (m, 2 H), 0.89 (quin, J = 3.6 Hz, 2 H), 1.21-1.34 (m, 1 H),1.73- 1.83 (m, 2 H), 1.83-1.94 (m, 2 H), 2.78- 2.94 (m, 1 H), 3.58 (dd,J = 9.8, 5.7 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H), 3.86-4.05 (m, 3 H),4.17-4.33 (m, 4 H), 7.31-7.38 (m, 1 H), 7.52 (d, J = 11.0 Hz, 1 H),7.56- 7.66 (m, 2 H), 7.76 (d, J = 8.7 Hz, 1 H), 7.93 (d, J = 4.8 Hz, 2H). MS m/z 272.2 (M + H)+ 228

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(6-fluoroquinolin-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.60-0.72 (m, 2 H), 0.86 (quin, J = 3.6 Hz, 2 H),1.26 (td, J = 8.1, 3.9 Hz, 1 H), 1.73-1.84 (m, 2 H), 1.84-1.93 (m, 2 H),2.73-2.91 (m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1 H), 3.70-3.82 (m, 1 H),3.85- 4.01 (m, 3 H), 4.22 (t, J = 8.3 Hz, 1 H), 7.41-7.58 (m, 2 H), 7.67(t, J = 7.6 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 1 H), 8.02-8.20 (m, 3 H),8.23 (d, J = 8.7 Hz, 1 H). MS m/z 487.2 (M + H)+ 229

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)quinolin-2- carbonitrile ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.68 (dd, J = 6.8, 4.2 Hz, 2 H), 0.88 (t, J = 3.6Hz, 2 H), 1.26-1.36 (m, 1 H), 1.74- 1.85 (m, 2 H), 1.85-1.96 (m, 2 H),2.76- 2.99 (m, 1 H), 3.54 (d, J = 5.5 Hz, 1 H), 3.80 (d, J = 6.6 Hz, 1H), 3.86-4.07 (m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.60 (d, J = 10.9 Hz,1 H), 7.64-7.73 (m, 2 H), 7.77 (d, J = 8.4 Hz, 1 H), 8.03-8.17 (m, 2 H),8.30 (d, J = 8.7 Hz, 1 H), 8.39 (d, J = 8.5 Hz, 1 H). MS m/z 494 (M +H)+ 230

(R)-5-(4-(benzo[b]thiophen-5-yl)-3- methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.57-0.77 (m, 2 H), 0.79-1.00 (m, 2 H), 1.39-1.53(m, 1 H), 1.65-1.75 (m, 2 H), 1.76-1.87 (m, 2 H), 1.89-2.04 (m, 1 H),2.28 (s, 3 H), 2.44-2.60 (m, 1 H), 3.00 (dd, J = 11.8, 7.1 Hz, 0.5 H),3.14- 3.33 (m, 1 H), 3.36-3.61 (m, 3.5 H), 3.69- 3.86 (m, 2 H),7.17-7.40 (m, 4 H), 7.40- 7.57 (m, 2 H), 7.70 (s, 1 H), 7.87 (d, J = 8.1Hz, 1 H). MS m/z 484 (M + H)+ 231

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzo[b]thiophen-5-yl)-3-methylphenyl)-4,6-diazaspiro[2.4]hept-4- em-7-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.68 (br. s., 4 H), 1.47 (d, J = 7.4 Hz, 1 H), 1.61 (br.s., 2 H), 1.66 (br. s., 0.5 H), 1.79 (d, J = 3.8 Hz, 2 H), 1.89 (d, J =5.5 Hz, 0.5 H), 2.32 (d, J = 8.5 Hz, 6 H), 2.45 (br s, 1 H), 2.50 (br.s., 3 H), 2.87-3.00 (m, 0.5 H), 3.10-3.23 (m, 1 H), 3.29 (br. s., 1 H),3.44-3.58 (m, 2.5 H), 3.71-3.87 (m, 2 H), 7.31 (d, J = 8.1 Hz, 1 H),7.44 (d, J = 7.8 Hz, 1 H), 7.62 (br. s., 3 H), 7.93 (d, J = 8.1 Hz, 1H). MS m/z 512 (M + H)+ 232

(R)-5-(4-(benzofuran-5-yl)-3- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.67 (br. s., 4 H), 1.45 (br s., 0.5 H), 1.63 (br. s., 3.5 H),1.76-1.85 (m, 2 H), 1.90 (br s., 1 H), 2.22-2.45 (m, 1 H), 2.88- 2.95(m, 0.5 H), 3.19 (d, J = 5.9 Hz, 1 H), 3.60 (br. s., 2.5 H), 3.78 (br.s., 2 H), 7.06 (br. s., 1 H), 7.56 (d, J = 8.4 Hz, 1 H), 7.61- 7.81 (m,4 H), 7.92 (br. s., 1 H), 8.08 (s, 1 H). MS m/z 472 (M + H)+ 233

(R)-5-(4-(benzo[b]thiophen-5-yl)-3- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.65 (dd, J = 7.6, 3.1 Hz, 2 H), 0.83- 0.95 (m, 2H), 1.44 (td, J = 8.0, 4.3 Hz, 1 H), 1.63 (dd, J = 12.6, 7.8 Hz, 1 H),1.69- 1.76 (m, 2 H), 1.76-1.84 (m, 2 H), 1.84- 2.01 (m, 1 H), 2.28-2.58(m, 1 H), 3.01 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.15-3.34 (m, 1 H),3.43-3.83 (m, 4.5 H), 7.34 (d, J = 5.4 Hz, 1 H), 7.36-7.53 (m, 4 H),7.54- 7.66 (m, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.97 (s, 1 H). MS m/z488 (M + H)+ 234

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-fluoro-4-(1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.65 (dd, J = 7.8, 3.0 Hz, 2 H), 0.83- 0.97 (m, 2H), 1.41-1.51 (m, 1 H), 1.55- 1.68 (m, 1 H), 1.68-1.76 (m, 2 H), 1.76-1.84 (m, 2 H), 1.84-1.91 (m, 1 H), 2.29- 2.58 (m, 1 H), 3.02 (dd, J =12.0, 6.9 Hz, 0.5 H), 3.14-3.35 (m, 1 H), 3.43-3.67 (m, 2.5 H),3.67-3.85 (m, 2 H), 5.54 (br. s., 1 H), 6.53 (br. s., 1 H), 7.28-7.45(m, 4 H), 7.52-7.67 (m, 1 H), 7.79 (s, 1 H), 8.77 (br. s., 1 H). MS m/z471 (M + H)+ 235

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(pyridin-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.68-0.81 (m, 2 H), 0.95 (dt, J = 7.1, 3.6 Hz, 2 H),1.47-1.58 (m, 1 H), 1.77- 1.93 (m, 4 H), 1.96-2.11 (m, 1 H), 2.37- 2.52(m, 1 H), 2.58 (d, J = 7.6 Hz, 1 H), 3.06 (dd, J = 12.0, 7.1 Hz, 0.5 H),3.23- 3.41 (m, 1 H), 3.49-3.74 (m, 2.5 H), 3.78- 3.89 (m, 2 H), 7.58 (d,J = 5.9 Hz, 2 H), 7.67-7.76 (m, 2 H), 7.76-7.89 (m, 6 H), 8.71 (d, J =5.5 Hz, 2 H). MS m/z 491 (M + H)+ 236

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-fluoro-4-(1H-indol-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.57-0.74 (m, 4 H), 1.38-1.57 (m, 1 H), 1.57-1.68 (m, 3 H),1.71-1.84 (m, 2 H), 1.84-1.97 (m, 1 H), 2.22-2.36 (m, 1 H), 2.92 (dd, J= 11.8, 6.8 Hz, 0.5 H), 3.11- 3.24 (m, 1 H), 3.24-3.32 (m, 1 H), 3.46-3.66 (m, 1.5 H), 3.78 (t, J = 6.5 Hz, 2 H), 6.50 (br. s., 1 H), 7.26 (d,J = 8.1 Hz, 1 H), 7.46 (br. s., 1 H), 7.59-7.80 (m, 5 H), 11.28 (br. s.,1 H). MS m/z 471 (M + H)+ 237

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-fluoro-4-(1H-indazol-4-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.61-0.70 (m, 4 H), 1.41-1.60 (m, 1 H), 1.64 (br. s., 3 H),1.80-1.85 (m, 2 H), 1.92 (d, J = 6.3 Hz, 1 H), 2.26-2.38 (m, 0.5 H),2.38-2.48 (m, 0.5 H), 2.92 (dd, J = 11.8, 6.7 Hz, 0.5 H), 3.11-3.31 (m,2 H), 3.46-3.66 (m, 1.5 H), 3.80 (t, J = 6.7 Hz, 2 H), 7.27 (d, J = 6.7Hz, 1 H), 7.50 (t, J = 7.7 Hz, 1 H), 7.61-7.75 (m, 3 H), 7.75- 7.85 (m,2 H), 8.00 (br. s., 1 H), 13.29 (br. s., 1 H). MS m/z 472 (M + H)+ 238

(R)-5-(4-(1H-indol-5-yl)-3-methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.68 (br. s., 4 H), 1.35-1.56 (m, 1 H), 1.56-1.69 (m, 3 H), 1.78(d, J = 3.8 Hz, 2 H), 1.89 (dd, J = 12.4, 6.1 Hz, 1 H), 2.27- 2.35 (m, 3H), 2.43 (d, J = 13.6 Hz, 1 H), 2.94 (dd, J = 11.8, 6.7 Hz, 0.5 H),3.10- 3.23 (m, 1 H), 3.23-3.33 (m, 1 H), 3.45- 3.63 (m, 1.5 H), 3.77 (t,J = 7.4 Hz, 2 H), 6.48 (br. s., 1 H), 7.11 (d, J = 8.2 Hz, 1 H),7.34-7.44 (m, 2 H), 7.44-7.66 (m, 4 H), 11.20 (br. s., 1 H). MS m/z 467(M + H)+ 239

(R)-5-(4-(1H-indol-6-yl)-3-methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.61-0.74 (m, 4 H), 1.39-1.53 (m, 0.5 H), 1.54-1.68 (m, 3.5 H),1.73-1.95 (m, 3 H), 2-27-2.48 (m, 1 H), 2.35 (s, 3 H), 2.88-3.00 (m, 0.5H), 3.11-3.23 (m, 1 H), 3.25-3.42 (m, 1 H), 3.46-3.63 (m, 1.5 H), 3.77(t, J = 7.3 Hz, 2 H), 6.49 (br s, 1 H), 7.02 (d, J = 8.0 Hz, 1 H),7.35-7.45 (m, 3 H), 755-7.68 (m, 3 H), 11.19 (br s, 1H). MS m/z 467 (M +H)+ 240

(R)-5-(4-(benzofuran-5-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.58-0.71 (m, 4 H), 1.35-1.68 (m, 4 H), 1.72-1.92 (m, 3 H),2.21-2.33 (m, 1 H), 2.87 (dd, J = 11.7, 7.0 Hz, 0.5 H), 3.08- 3.31 (m, 2H), 3.41-3.53 (m, 1.5 H), 3.53- 3.63 (m, 2 H), 7.05 (d, J = 1.8 Hz, 1H), 7.68-7.88 (m, 5 H), 8.04-8.14 (m, 2 H). MS m/z 472 (M + H)+ 241

(R)-5-(4-(benzo[b]thiophen-5-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.58-0.72 (m, 4 H), 1.35-1.70 (m, 4 H), 1.70-1.95 (m, 3 H), 2.29(d, J = 7.0 Hz, 0.5 H), 2.38 (br. s., 0.5 H), 2.87 (dd, J = 11.7, 6.9Hz, 0.5 H), 3.07-3.32 (m, 2 H), 3.47 (t, J = 6.9 Hz, 1 H), 3.53-3.64 (m,2.5 H), 7.55 (d, J = 5.4 Hz, 1 H), 7.73- 7.93 (m, 5 H), 8.15 (d, J = 8.4Hz, 1 H), 8.35 (s, 1 H). MS m/z 488 (M + H)+ 242

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(2- methylbenzofuran-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.74(m, 4 H), 1.31-1.68 (m, 4 H), 1.79-1.94 (m, 3 H), 2.19-2.34 (m, 1 H),2.48 (s, 3 H), 2.86 (dd, J = 11.8, 7.1 Hz, 0.5 H), 3.07-3.32 (m, 2 H),3.43-3.51 (m, 1 H), 3.51-3.63 (m, 2.5 H), 6.66 (s, 1 H), 7.56-7.68 (m, 5H), 7.96 (s, 1 H). MS m/z 486 (M + H)+ 243

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.72(m, 4 H), 1.33-1.69 (m, 4 H), 1.69-1.94 (m, 3 H), 2.20-2.33 (m, 0.5 H),2.33-2.47 (m, 0.5 H), 2.60 (s, 3 H), 2.86 (dd, J = 11.8, 6.9 Hz, 0.5 H),3.06- 3.32 (m, 2 H), 3.41-3.51 (m, 1 H), 3.51- 3.64 (m, 2.5 H), 7.21 (s,1 H), 7.65-7.90 (m, 4 H), 8.00 (d, J = 8.4 Hz, 1 H), 8.17 (s, 1 H). MSm/z 502 (M + H)+ 244

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-2-fluorophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.57-0.75(m, 4 H), 1.32-1.52 (m, 1 H), 1.52-1.69 (m, 3 H), 1.69-1.95 (m, 3 H),2.21 (s, 3 H), 2.24-2.38 (m, 1 H), 2.41 (s, 3 H), 2.86 (dd, J = 11.7,7.0 Hz, 0.5 H), 3.05-3.32 (m, 2 H), 3.42-3.51 (m, 1 H), 3.51-3.64 (m,2.5 H), 7.50-7.60 (m, 1 H), 7.62-7.90 (m, 4 H), 7.94 (s, 1 H). MS m/z500 (M + H)+ 245

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzo[b]thiophen-5-yl)-2-fluorophenyl)-4,6-diazaspiro}2.4[hept-4- en-7-one] ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.31-0.46 (m, 4 H), 1.07-1.43 (m, 4 H), 1.45-1.69 (m, 3H), 1.94-2.09 (m, 1 H), 2.12 (s, 3 H), 2.25 (s, 3 H), 2.62 (dd, J =11.8, 6.9 Hz, 0.5 H), 2.82-3.07 (m, 2 H), 3.12-3.27 (m, 1.5 H),3.28-3.39 (m, 2 H), 7.42-7.76 (m, 5 H), 7.82 (s, 1 H). MS m/z 516 (M +H)+ 246

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.56-0.73 (m, 4 H), 1.49-1.68 (m, 4 H), 1.68-1.95 (m, 3 H), 2.28(br. s., 0.5 H), 2.37 (br. s., 0.5 H), 2.87 (dd, J = 11.8, 6.9 Hz, 0.5H), 3.07-3.29 (m, 2 H), 3.43- 3.52 (m, 1 H), 3.58 (br. s., 2.5 H), 6.53(br. s., 1 H), 7.42 (t, J = 2.5 Hz, 1 H), 7.46- 7.59 (m, 2 H), 7.61-7.83(m, 3 H), 8.01 (s, 1 H), 11.27 (br. s., 1 H). MS m/z 471 (M + H)+ 247

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1H-indol-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.57-0.71 (m, 4 H), 1.33-1.60 (m, 2 H), 1.60-1.68 (m, 2 H),1.79-1.94 (m, 3 H), 2.22-2.35 (m, 0.5 H), 2.35-2.48 (m, 0.5 H), 2.88(dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07- 3.32 (m, 2 H), 3.39-3.52 (m, 1.5H), 3.58 (t, J = 8.3 Hz, 2 H), 6.50 (br. s., 1 H), 7.40-7.49 (m, 2 H),7.63-7.84 (m, 5 H), 11.30 (br. s., 1 H). MS m/z 471 (M + H)+ 248

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(quinolin-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.54-0.72 (m, 4 H), 1.37-1.68 (m, 4 H), 1.71-1.93 (m, 3 H),2.21-2.48 (m, 1 H), 2.82-2.92 (m, 0.5 H), 3.06-3.32 (m, 2 H), 3.43-3.53(m, 1 H), 3.53-3.66 (m, 2.5 H), 7.61 (dd, J = 8.2, 4.1 Hz, 1 H), 7.82(dt, J = 11.7, 7.7 Hz, 1 H), 7.88-8.04 (m, 2 H), 8.15 (d, J = 8.7 Hz, 1H), 8.23 (d, J = 8.7 Hz, 1 H), 8.40-8.54 (m, 2 H), 8.87-9.06 (m, 1 H).MS m/z 483 (M + H)+ 249

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(quinolin-7-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.56-0.70 (m, 4 H), 1.36-1.70 (m, 4 H), 1.70-1.96 (m, 3 H),2.22-2.36 (m, 1 H), 2.88 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06- 3.32 (m, 2H), 3.47 (t, J = 7.1 Hz, 1 H), 3.52-3.66 (m, 2.5 H), 7.59 (dd, J = 8.2,4.3 Hz, 1 H), 7.81 (dt, J = 11.9, 7.7 Hz, 1 H), 7.89-8.18 (m, 4 H),8.39-8.51 (m, 2 H), 8.89-9.06 (m, 1 H). MS m/z 483 (M + H)+ 250

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(quinolin-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.67 (d, J = 6.0 Hz, 4 H), 1.45 (dd, J = 12.5, 7.3 Hz, 1 H),1.57-1.71 (m, 3 H), 1.74- 1.88 (m, 2 H), 1.88-2.01 (m, 1 H), 2.23- 2.42(m, 1 H), 2.88 (dd, J = 11.6, 6.9 Hz, 0.5 H), 3.10-3.31 (m, 2 H), 3.51(t, J = 6.5 Hz, 1 H), 3.56-3.70 (m, 2.5 H), 7.46- 7.73 (m, 4 H),7.76-7.96 (m, 2 H), 8.14 (d, J = 8.4 Hz, 1 H), 8.27 (dd, J = 15.9, 8.6Hz, 1 H), 8.98 (d, J = 3.4 Hz, 1 H). MS m/z 483 (M + H)+ 251

(R)-5-(4-(benzo[d]oxazol-2-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.51-0.75 (m, 4 H), 1.32-1.71 (m, 4 H), 1.71-1.94 (m, 3 H),2.18-2.32 (m, 1 H), 2.85 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.05- 3.30 (m, 2H), 3.41-3..53 (m, 1 H), 3.53- 3.66 (m, 2.5 H), 7.42-7.57 (m, 2 H),7.97- 8.00 (m, 3 H), 8.11-8.29 (m, 2 H). MS m/z 473 (M + H)+ 252

(R)-5-(4-(benzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.55-0.73 (m, 4 H), 1.32-1.53 (m, 1 H), 1.58 (dd, J = 5.7, 2.3 Hz,1 H), 1.63-1.70 (m, 2 H), 1.77 (br. s., 1 H), 1.81-1.95 (m, 2 H),2.21-2.33 (m, 1 H), 2.86 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06-3.31 (m, 2H), 3.42-3.53 (m, 1 H), 3.53-3.66 (m, 2.5 H), 7.48-7.66 (m, 2 H), 7.88(dt, J = 12.7, 7.7 Hz, 1 H), 8.06-8.18 (m, 3 H), 8.23 (d, J = 7.8 Hz, 1H). MS m/z 489 (M + H)+ 253

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.54-0.72 (m, 4 H), 1.35-1.69 (m, 4 H), 1.69-1.95 (m, 3 H),2.17-2.33 (m, 0.5 H), 2.33-2.46 (m, 0.5 H), 2.87 (dd, J = 11.8, 6.9 Hz,0.5 H), 3.05-3.31 (m, 2 H), 3.43-3.52 (m, 1 H), 3.52-3.67 (m, 2.5 H),7.54-7.91 (m, 5 H), 8.23 (s, 1 H), 8.18 (s, 1 H), 13.23 (br. s., 1 H).MS m/z 472 (M + H)+ 254

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)benzofuran-2- carbonitrile ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.56-0.72 (m, 4 H), 1.47-1.69 (m, 4 H), 1.69-1.94 (m, 3H), 2.20-2.33 (m, 0.5 H), 2.40 (d, J = 7.0 Hz, 0.5 H), 2.86 (dd, J =11.8, 7.0 Hz, 0.5 H), 3.06-3.31 (m, 2 H), 3.43-3.52 (m, 1 H), 3.52-3.64(m, 2.5 H), 7.73-7.82 (m, 2 H), 7.83-7.94 (m, 2 H), 8.05 (d, J = 9.1 Hz,1 H), 8.20 (s, 1 H), 8.28 (s, 1 H). MS m/z 497 (M + H)+ 255

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-methylphenyl)benzofuran-2- carbonitrile ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.42 (d, J = 5.2 Hz, 4 H), 1.07-1.28 (m, 1 H), 1.38 (br.s., 3 H), 1.45-1.71 (m, 3 H), 1.91-2.11 (m, 1 H), 2.15 (br. s., 3 H),2.62 (dd, J = 11.3, 6.7 Hz, 0.5 H), 2.80- 3.06 (m, 2 H), 3.16-3.36 (m,3.5 H), 7.36 (dd, J = 13.0, 8.0 Hz, 1 H), 7.47 (br. s., 1 H), 7.554 (br.s., 1 H), 7.63 (d, J = 8.7 Hz, 1 H), 7.75 (d, J = 8.7 Hz, 1 H), 7.95 (d,J = 7.1 Hz, 2 H). MS m/z 493 (M + H)+ 256

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)benzofuran-2-carbonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.71 (m, 4 H),1.37-1.67 (m, 4 H), 1.69-1.94 (m, 3 H), 2.20-2.33 (m, 0.5 H), 2.38 (d, J= 6.9 Hz, 0.5 H), 2.90 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07-3.31 (m, 2H), 3.40-3.62 (m, 1.5 H), 3.77 (t, J = 6.3 Hz, 2 H), 7.79-7.95 (m, 5 H),7.95-8.04 (m, 1 H), 8.18 (s, 1 H), 8.21 (s, 1 H). MS m/z 479 (M + H)+257

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(quinolin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62-0.83 (m, 2 H), 0.85-1.07 (m, 2 H), 1.39-1.60(m, 1 H), 1.60-1.77 (m, 1 H), 1.80-2.08 (m, 5 H), 2.38-2.53 (m, 1 H),2.92-3.10 (m, 0.5 H), 3.18-3.41 (m, 1 H), 3.50-3.83 (m, 4.5 H), 7.54-7.88 (m, 5 H), 7.93 (d, J = 7.8 Hz, 1 H), 8.18 (d, J = 8.5 Hz, 1 H),8.33-8.50 (m, 1 H), 9.20 (d, J = 2.3 Hz, 1 H). MS m/z 483 (M + H)+ 258

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(quinazolin-7-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.50-0.71 (m, 2 H), 0.72-0.95 (m, 2 H), 1.34-1.49(m, 1 H), 1.51-1.68 (m, 1 H), 1.68-1.79 (m, 2 H), 1.79-1.88 (m, 2 H),1.89-2.02 (m, 1 H), 2.29-2.44 (m, 0.5 H), 2.44-2.61 (m, 0.5 H), 2.90(dd, J = 12.0, 7.3 Hz, 0.5 H), 3.10-3.31 (m, 1 H), 3.40-3.58 (m, 2.5 H),3.59-3.76 (m, 2 H), 7.54 (dd, J = 10.9, 5.9 Hz, 1 H), 7.59- 7.71 (m, 21H), 7.87 (d, J = 8.4 Hz, 1 H), 8.01 (d, J = 8.4 Hz, 1 H), 8.22 (s, 1 H),9.32 (s, 1 H), 9.40 (s, 1 H). MS m/z 484 (M + H)+ 259

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(6- fluoronaphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.55-0.70 (m, 2 H), 0.75-0.94 (m, 2 H), 1.34-1.48 (m, 1.5 H), 1.52-1.63(m, 0.5 H), 1.69-1.76 (m, 2 H), 1.78- 1.87 (m, 2 H), 1.87-2.01 (m, 1 H),2.36 (dt, J = 14.5, 7.3 Hz, 1 H), 2.90 (dd, J = 12.0, 7.3 Hz, 0.5 H),3.09-3.30 (m, 1 H), 3.37-3.58 (m, 2.5 H), 3.58-3.72 (m, 2 H), 7.26 (td,J = 8.7, 2.0 Hz, 1 H), 7.38- 7.53 (m, 2 H), 7.58 (d, J = 3.8 Hz, 2 H),7.68 (d, J = 8.2 Hz, 1 H), 7.79-7.90 (m, 2 H), 8.01 (s, 1 H). MS m/z 500(M + H)+ 260

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(8- fluoronaphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.40-0.56 (m, 2 H), 0.70 (br. s., 2 H), 1.18-1.33 (m, 1.5 H), 1.36-1.51(m, 0.5 H), 1.55-1.63 (m, 2 H), 1.64-1.72 (m, 2 H), 1.73-1.87 (m, 1 H),2.20-2.38 (m, 1 H), 2.77 (dd, J = 11.8, 7.3 Hz, 0.5 H), 2.93-3.17 (m, 1H), 3.22-3.44 (m, 2.5 H), 3.44-3.62 (m, 2 H), 6.93-7.10 (m, 1 H),7.17-7.31 (m, 1 H), 7.32-7.42 (m, 1 H), 7.46 (d, J = 6.7 Hz, 3 H), 7.57(d, J = 8.7 Hz, 1 H), 7.76 (d, J = 8.5 Hz, 1 H), 8.13 (s, 1 H). MS m/z500 (M + H)+ 261

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1H-indol-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.54-0.71 (m, 2 H), 0.74-0.95 (m, 2 H), 1.32-1.49(m, 1.5 H), 1.54-1.66 (m, 1 H), 1.68-1.76 (m, 2 H), 1.77-1.85 (m, 2 H),1.86-2.01 (m, 0.5 H), 2.28- 2.59 (m, 1 H), 2.94 (dd, J = 12.0, 7.1 Hz,0.5 H), 3.09-3.31 (m, 1 H), 3.42-3.59 (m, 2.5 H), 3.59-3.72 (m, 2 H),7.06- 7.27 (m, 2 H), 7.40 (d, J = 2.9 Hz, 1 H), 7.37 (d, J = 2.2 Hz, 1H), 7.42-7.58 (m, 3 H), 7.86 (d, J = 7.6 Hz, 1 H), 8.93 (d, J = 6.6 Hz,1 H). MS m/z 471 (M + H)+ 262

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.71(dd, J = 4.7, 3.0 Hz, 2 H), 0.90- 1.01 (m, 2 H), 1.43-1.56 (m, 1.5 H),1.59- 1.74 (m, 0.5 H), 1.76-1.83 (m, 2 H), 1.84-1.89 (m, 2 H), 1.89-2.08(m, 1 H), 2.43 (s, 3 H), 2.45-2.60 (m, 1 H), 3.00 (dd, J = 12.0, 6.9 Hz,0.5 H), 3.15-3.39 (m, 1 H), 3.41-3.73 (m, 4.5 H), 4.14 (s, 3 H), 7.43(d, J = 7.8 Hz, 1 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.55-7.63 (m, 2 H),7.65-7.73 (m, 1 H), 7.98 (s, 1 H), 8.06 (s, 1 H). MS m/z 482 (M + H)+263

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.36-0.52 (m, 2 H), 0.59-0.71 (m, 2 H), 0.98-1.11(m, 2 H), 1.42-1.57 (m, 2 H), 1.57-1.76 (m, 3 H), 2.15 (s, 3 H), 2.22(s, 3 H), 2.50 (dd, J = 7.6, 6.4 Hz, 1 H), 3.27-3.37 (m, 1 H), 3.38-3.51(m, 1 H),. 3.51-3.66 (m, 2 H), 3.66-3.78 (m, 1 H), 3.96 (t, J = 8.2 Hz,1 H), 6.03 (s, 1 H), 7.04-7.17 (m, 3 H), 7.26-7.42 (m, 2 H), 7.51 (s, 1H), 8.19 (br. s., 1 H). MS m/z 467 (M + H)+ 264

5-(2-chloro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.42-0.52 (m, 2 H), 0.70 (d, J = 3.2 Hz, 2 H), 1.34-1.44 (m, 2 H),1.51-1.63 (m, 2 H), 2.30-2.44 (m, 1 H), 3.19 (br. s., 1 H), 3.46 (t, J =6.9 Hz, 2 H), 3.55 (br. s., 1 H), 3.79 (br. s., 1 H), 3.86 (s, 3 H),4.14 (br. s., 1 H), 5.66 (br. s., 1 H), 7.47-7.58 (m, 2 H), 7.59-7.70(m, 2 H), 7.80 (s, 1 H), 7.90 (s, 1 H), 7.99 (s, 1 H). MS m/z 504 (M +H)+ 265

(R)-5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.40 (br. s., 2 H), 0.57-0.83 (m, 2 H), 1.10 (br. s., 4 H), 1.43(br. s., 1 H), 1.61 (br. s., 2 H), 1.79 (br. s., 3 H), 2.27 (br. s., 1H), 2.39 (br. s., 3 H), 2.99 (br. s., 1 H), 3.18 (br. s., 2 H), 3.48(br. s., 3 H), 4.10 (br. s., 3 H), 7.57 (br. s., 1 H), 7.79 (br. s., 4H), 8.13 (br. s., 2 H). MS m/z 496 (M + H)+ 266

(R)-5-(4-(6-fluoronaaphthalen-2-yl)-2- methylphenyl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.27 (br. s., 2 H), 0.59 (t, J = 10.7 Hz, 2 H), 0.97 (s, 3 H),1.30 (br. s., 1 H), 1.43- 1.53 (m, 2 H), 1.67 (d, J = 4.0 Hz, 3 H), 2.13(br. s., 1 H), 2.28 (s, 3 H), 2.80 (d, J = 19.2 Hz, 1 H), 2.98-3.18 (m,1.5 H), 3.24-3.30 (m, 1 H), 3.35 (br. s., 2.5 H), 7.31-7.41 (m, 1 H),7.43-7.53 (m, 1 H), 7.60-7.72 (m, 2 H), 7.76 (s, 1 H), 7.85 (d, J = 8.7Hz, 1 H), 7.92 (d, J = 8.7 Hz, 1 H), 8.00 (dd, J = 9.0, 5.8 Hz, 1 H),8.26 (s, 1 H). MS m/z 510 (M + H)+ 267

(R)-5-(3-methyl-4-(1-methyl-1H-pyrazol-4-yl)-[1,1-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 522 (M + H)+ 268

2-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-fluorophenyl)benzo[d]thiazole-6- carbonitrile ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62 (dd, J = 7.4, 3.2 Hz, 2 H), 0.77- 0.88 (m, 2H), 1.22 (td, J = 7.9, 1.4 Hz, 1 H), 1.70-1.80 (m, 2 H), 1.80-1.90 (m, 2H), 2.69-2.85 (m, 1 H), 3.39-3.50 (m, 1 H), 3.63-3.76 (m, 1 H),3.81-3.95 (m, 3 H), 4.19 (t, J = 8.2 Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1 H), 7.91- 8.04 (m, 2 H), 8.12 (d, J = 8.5 Hz,1 H), 8.23 (s, 1 H). MS m/z 500 (M + H)+ 269

6-(3-methyl-4-(6-((1-(1- methylcyclopropanecarbbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.44 (br. s., 2 H), 0.98 (br. s., 2 H), 1.20 (br. s., 3 H), 1.76 (br.s., 1 H), 1.82 (br. s., 2 H), 1.89 (br. s., 2 H), 2.47 (br. s., 3 H),2.77 (br. s., 1 H), 3.49 (br. s., 1 H), 3.70-3.82 (m, 2 H), 4.14 (br.s., 2 H), 7.50 (d, J = 7.3 Hz, 1 H), 7.71 (d, J = 6.3 Hz, 3 H), 7.90 (d,J = 8.0 Hz, 1 H), 7.96- 8.08 (m, 2 H), 8.13 (br. s., 1 H), 8.29 (br. s.,1 H). MS m/z 503 (M + H)+ 270

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6-methylbenzo[d]thiazol-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.46 (br. s., 2 H), 0.66 (br. s., 2H), 1.06 (br. s., 1 H), 1.59 (br. s., 2 H), 1.67 (br. s., 2 H), 2.30(br. s., 3 H), 2.59 (br. s., 1 H), 3.34 (br. s., 1 H), 3.46-3.62 (m, 1H), 3.71 (br. s., 3 H), 4.01 (br. s., 1 H), 7.13 (d, J = 7.7 Hz, 1 H),7.44 (br. s., 1 H), 7.52 (br. s., 1 H), 7.66-7.95 (m, 3 H). MS m/z 489(M + H)+ 271

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6-fluorobenzo[d]thiazol-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.71 (br. s., 2 H), 0.91 (br. s., 2H), 1.31 (br. s., 1 H), 1.82 (br. s., 2 H), 1.92 (br. s., 2 H), 2.84(br. s., 1 H), 3.57 (br. s., 1 H), 3.81 (d, J = 5.6 Hz, 1 H), 3.97 (d, J= 7.7 Hz, 3 H), 4.26 (br. s., 1 H), 7.29 (br. s., 1 H), 7.56-7.79 (m, 2H), 7.86-8.20 (m, 3 H). MS m/z 493 (M + H)+ 272

6-(4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.81 (br. s., 2 H),1.12 (br. s., 2 H), 1.71 (br. s., 2 H), 1.79 (br. s., 2 H), 2.54- 2.75(m, 1 H), 3.47 (br. s., 1 H), 3.68 (br. s., 2 H), 3.80-4.17 (m, 2 H),4.35 (br. s., 1 H), 7.39 (d, J = 7.7 Hz, 1 H), 7.54-7.66 (m, 3 H), 7.81(d, J = 8.5 Hz, 1 H), 7.92 (dd, J = 8.1, 3.0 Hz, 2 H), 8.04 (s, 1 H),8.20 (s, 1 H). MS m/z 505 (M + H)+ 273

6-(4-(6-((1-(1- fluorocyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.97-1.15 (m, 2 H),1.15-1.28 (m, 2 H), 1.68-1.76 (m, 2 H), 1.76-1.86 (m, 2 H), 2.67-2.85(m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1 H), 3.70 (t, J = 6.7 Hz, 2 H),3.87-4.03 (m, 2 H), 4.32 (br. s., 1 H), 7.40 (d, J = 7.8 Hz, 1 H),7.54-7.67 (m, 3 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.93 (dd, J = 8.5, 3.9Hz, 2 H), 8.05 (s, 1 H), 8.20 (s, 1 H). MS m/z 507 (M + H)+ 274

5-(4-(6-chlorobenzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.2, 3.1 Hz, 2 H), 0.81 (br. s., 2 H),1.21 (td, J = 7.8, 3.8 Hz, 1 H), 1.68-1.79 (m, 2 H), 1.79-1.89 (m, 2 H),2.65-2.86 (m, 1 H), 3.39-3.55 (m, 1 H), 3.71 (d, J = 6.6 Hz, 1 H),3.76-3.98 (m, 3 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.37-7.49 (m, 1 H), 7.61(t, J = 7.5 Hz, 1 H), 7.86 (s, 1 H), 7.88-8.04 (m, 3 H). MS m/z 509 (M +H)+ 275

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-fluoroquinolin-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62-0.76 (m, 2 H), 0.85-0.98 (m, 2 H), 1.20-1.40(m, 1 H), 1.79-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.74-2.93 (m, 1 H),3.61 (dd, J = 9.6, 5.5 Hz, 1 H), 3.88- 4.04 (m, 3 H), 4.04-4.15 (m, 1H), 4.23 (t, J = 8.2 Hz, 1 H), 7.43-7.62 (m, 2 H), 7.76 (d, J = 8.2 Hz,2 H), 7.97 (d, J = 8.5 Hz, 1 H), 8.14-8.30 (m, 2 H), 8.34 (d, J = 8.2Hz, 2 H). MS m/z 469 (M + H)+ 276

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)quinolin-2-carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d)δ ppm 0.62 (dd, J = 7.1, 4.0 Hz, 2 H), 0.82 (t, J = 3.6 Hz, 2 H),1.14-1.30 (m, 1 H), 1.70- 1.77 (m, 2 H), 1.77-1.87 (m, 2 H), 2.70- 2.87(m, 1 H), 3.51 (dd, J = 9.6, 5.5 Hz, 1 H), 3.81-3.96 (m, 3 H), 3.96-4.10(m, 1 H), 4.18 (t, J = 8.2 Hz, 1 H), 7.62-7.74 (m, 3 H), 7.82 (d, J =8.1 Hz, 2 H), 8.00-8.12 (m, 2 H), 8.15-8.26 (m, 1 H), 8.31 (d, J = 8.5Hz, 1 H). MS m/z 476 (M + H)+ 277

2-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)quinoline-6-carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d)δ ppm 0.51-0.71 (m, 2 H), 0.82 (br. s., 2 H), 1.14-1.27 (m, 1 H), 1.64(br. s., 2 H), 1.73 (br. s., 2 H), 2.75 (br. s., 1 H), 3.51 (br. s., 1H), 3.75-3.95 (m, 3 H), 3.95- 4.08 (m, 1 H), 4.08-4.25 (m, 1 H), 7.71(d, J = 7.8 Hz, 2 H), 7.83 (d, J = 8.5 Hz, 1 H), 7.99 (d, J = 8.5 Hz, 1H), 8.09-8.24 (m, 2 H), 8.24-8.44 (m, 3 H). MS m/z 509 (M + H)+ 278

(R)-5-(4-(benzofuran-5-yl)-2- methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.33-0.46 (m, 4 H), 1.10-1.28 (m, 1 H), 1.28-1.41 (m, 3 H),1.44-1.69 (m, 3 H), 1.91-2.10 (m, 1 H), 2.14 (s, 3 H), 2.62 (dd, J =11.7, 6.6 Hz, 0.5 H), 2.82-3.05 (m, 2 H), 3.15-3.37 (m, 3.5 H), 6.80 (s,1 H), 7.32 (dd, J = 13.0, 7.9 Hz, 1 H), 7.40- 7.50 (m, 3 H), 7.52 (br.s., 1 H), 7.79 (s, 1 H), 7.82 (d, J 1.9 Hz, 1 H). MS m/z 468 (M + H)+279

(R)-5-(4-(benzo[d]thiophen-5-yl)-2- methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.58-0.71 (m, 4 H), 1.39-1.65 (m, 4 H), 1.76-1.82 (m, 2 H),1.82-1.94 (m, 1 H), 2.23 (d, J = 6.6 Hz, 1 H), 2.39 (s, 3 H), 2.81-2.92(m, 0.5 H), 3.04-3.30 (m, 2 H), 3.47 (d, J = 7.1 Hz, 2.5 H), 3.55-3.66(m, 1 H), 7.51-7.63 (m, 2 H), 7.69-7.79 (m, 2 H), 7.83 (t, J = 5.3 Hz, 2H), 8.13 (d, J = 8.4 Hz, 1 H), 8.28 (s, 1 H). MS m/z 484 (M + H)+ 280

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(2- methylbenzofuran-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.73(m, 4 H), 1.43-1.65 (m, 4 H), 1.65-1.93 (m, 3 H), 2.13-2.33 (m, 1 H),2.37 (s, 3 H), 2.79-2.92 (m, 0.5 H), 3.04- 3.29 (m, 2 H), 3.37-3.62 (m,3.5 H), 6.65 (s, 1 H), 7.48-7.57 (m, 1 H), 7.57- 7.61 (m, 2 H),7.71-7.78 (m, 1 H), 7.89 (s, 1 H). MS m/z 482 (M + H)+ 281

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d,J = 5.8 Hz, 4 H), 1.34-1.49 (m, 1 H), 1.49-1.66 (m, 3 H), 1.68-1.84 (m,3 H), 2.24 (br. s., 1 H), 2.38 (s, 3 H), 2.60 (s, 3 H), 2.85 (d, J =11.7 Hz, 0.5 H), 3.04- 3.29 (m, 2 H), 3.36-3.53 (m, 2.5 H), 3.53- 3.62(m, 1 H), 7.22 (s, 1 H), 7.57 (dd, J = 13.4, 8.0 Hz, 1 H), 7.62-7.75 (m,2 H), 7.78 (br. s., 1 H), 7.98 (d, J = 8.4 Hz, 1 H), 8.10 (s, 1 H). MSm/z 498 (M + H)+ 282

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-2-methylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.46 (d,J = 5.5 Hz, 4 H), 1.14-1.35 (m, 1 H), 1.41 (br. s., 3 H), 1.49-1.64 (m,3 H), 1.64-1.75 (m, 1 H), 2.02 (s, 3 H), 2.18 (s, 3 H), 2.22 (s, 3 H),2.60-2.71 (m, 0.5 H), 2.86-3.00 (m, 1 H), 3.07 (br. s., 1 H), 3.15-3.42(m, 3.5 H), 7.29-7.44 (m, 3 H), 7.48 (br. s., 1 H), 7.57 (br. s., 1 H),7.65 (s, 1 H). MS m/z 496 (M + H)+ 283

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzo[b]thiophen-5-yl)-2-methylphenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.50-0.78 (m, 4 H), 1.32-1.48 (m, 1 H), 1.38-1.64 (m, 3H), 1.69-1.83 (m, 2 H), 1.83-1.94 (m, 1 H), 2.14-2.34 (m, 1 H), 2.38 (d,J = 5.4 Hz, 6 H), 2.81-2.93 (m, 0.5 H), 3.06-3.23 (m, 1 H), 3.28 (d, J =4.9 Hz, 1 H), 3.41-3.62 (m, 3.5 H), 7.57 (dd, J = 13.8, 7.9 Hz, 1 H),7.64-7.71 (m, 1 H), 7.74 (br. s., 1 H), 7.81-7.87 (m, 1 H), 7.93-8.03(m, 2 H). MS m/z 512 (M + H)+ 284

(R)-5-(4-(1H-indol-5-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.57-0.71 (m, 4 H), 1.44 (d, J = 7.4 Hz, 1 H), 1.60 (br. s., 3 H),1.78 (d, J = 3.8 Hz, 3 H), 1.87 (d, J = 6.0 Hz, 1 H), 2.25 (br. s., 1H), 2.37 (s, 3 H), 2.88 (br. s., 0.5 H), 3.05- 3.20 (m, 1 H), 3.26 (d, J= 7.0 Hz, 1 H), 3.43-3.53 (m, 2.5 H), 6.44-6.59 (m, 1 H), 7.40 (br. s.,1 H), 7.44-7.57 (m, 3 H), 7.64 (br. s., 1 H), 7.72 (br. s., 1 H), 7.93(s, 1 H), 11.18 (br. s., 1 H). MS m/z 467 (M + H)+ 286

(R)-5-(4-(1H-indazol-5-yl)-2- methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.32-0.51 (m, 4 H), 1.15 (d, J = 12.4 Hz, 1 H), 1.38 (br. s., 3H), 1.56 (d, J = 3.8 Hz, 2 H), 1.65 (br. s., 1 H), 2.02 (br. s., 1 H),2.15 (s, 3 H), 2.64 (dd, J = 11.9, 6.7 Hz, 0.5 H), 2.87-3.10 (m, 3.5 H),3.23 (br. s., 1 H), 3.25 (br. s., 1 H), 7.33 (dd, J = 13.1, 8.0 Hz, 1H), 7.39-7.50 (m, 2 H), 7.53 (d, J = 8.8 Hz, 2 H), 7.92 (d, J = 4.0 Hz,2 H), 12.3 (br. s., 1 H). MS m/z 468 (M + H)+ 287

5-(4-(benzofuran-5-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.55-0.68 (m, 4 H), 1.37 (t, J = 6.1 Hz, 1 H), 1.55-1.65 (m, 2 H),1.72-1.83 (m, 2 H), 2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J =9.6, 5.4 Hz, 1 H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.04(d, J = 1.9 Hz, 1 H), 7.56 (d, J = 8.0 Hz, 1 H), 7.66-7.74 (m, 3 H),7.77 (s, 1 H), 8.03 (s, 1 H), 8.06 (d, J = 2.1 Hz, 1 H). MS m/z 454 (M +H)+ 288

5-(4-benzo[b]thiophen-5-yl)-2- methylphenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.53-0.70 (m, 4 H), 1.29-1.44 (m, 1 H), 1.53-1.66 (m, 2 H),1.73-1.84 (m, 2 H), 2.37 (s, 3 H), 2.55-2.70 (m, 1 H), 3.33- 3.44 (m, 1H), 3.64-3.83 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 7.50-7.63 (m, 2 H),7.70-7.80 (m, 2 H), 7.80-7.88 (m, 2 H), 8.13 (d, J = 8.5 Hz, 1 H), 8.28(s, 1 H). MS m/z 470 (M + H)+ 289

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-methyl-4-(2-methylbenzofuran-5-yl)phenyl)-4,6- diazspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, DMSO-d₆) δ ppm 0.48-0.71 (m, 4 H), 1.26-1.46 (m, 1 H),1.54-1.65 (m, 2 H), 1.78 (d, J = 3.7 Hz, 2 H), 2.36 (s, 3 H), 2.48 (s, 3H), 2.54-2.68 (m, 1 H), 3.38 (br. s., 1 H), 3.61-3.83 (m, 4 H), 4.17 (t,J = 8.3 Hz, 1 H), 6.65 (s, 1 H), 7.51-7.63 (m, 3 H), 7.66 (s, 1 H), 7.75(s, 1 H), 7.89 (s, 1 H). MS m/z 468 (M + H)+ 290

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzo[b]thiophen-5-yl)-2-methylphenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.54-0.71 (m, 4 H), 1.37 (t, J = 6.0 Hz, 1 H), 1.55-1.65(m, 2 H), 1.74-1.84 (m, 2 H), 2.37 (s, 6 H), 2.47 9s, 3 H), 2.56- 2.69(m, 1 H), 3.39 (d, J = 5.5 Hz, 1 H), 3.70 (d, J = 7.4 Hz, 3 H), 3.79(br. s., 1 H), 4.17 (t, J = 8.2 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H),7.68 (d, J = 8.4 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 1 H), 7.84 (s, 1 H),7.92-8.04 (m, 2 H). MS m/z 498 (M + H)+ 291

5-(4-(1H-indol-5-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.53-0.71 (m, 4 H), 1.29-1.44 (m, 1 H), 1.51-1.64 (m, 2 H),1.71-1.84 (m, 2 H), 2.35 (s, 3 H), 2.54-2.69 (m, 1 H), 3.35- 3.44 (m, 1H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 6.52 (br. s., 1 H),7.40 (t, J = 2.6 Hz, 1 H), 7.44-7.54 (s, 1 H), 7.93 (s, 1 H), 11.19 (br.s., 1 H). MS m/z 453 (M + H)+ 292

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.71(m, 4 H), 1.31-1.43 (m, 1 H), 1.54-1.65 (m, 2 H), 1.72-1.83 (m, 2 H),2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J = 9.7, 5.6 Hz, 1 H),3.65-3.82 (m, 4 H), 4.10 (s, 3 H), 4.12-4.22 (m, 1 H), 7.56 (d, J = 8.0Hz, 1 H), 7.66-7.87 (m, 4 H), 8.13 (d, J = 3.6 Hz, 2 H). MS m/z 468 (M +H)+ 293

5-(4-(1H-indazol-5-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.52-0.71 (m, 4 H), 1.30-1.44 (m, 1 H), 1.53-1.65 (m, 2 H),1.72-1.84 (m, 2 H), 2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J =9.4, 5.4 Hz, 1 H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 7.55(d, J = 8.0 Hz, 1 H), 7.62-7.81 (m, 4 H), 8.15 (d, J = 3.6 Hz, 2 H),13.16 (br. s., 1 H). MS m/z 454 (M + H)+ 294

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methylbenzofuran-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.54-0.71 (m, 4 H), 1.35-1.50 (m, 1 H), 1.50-1.65 (m, 3 H),1.69-1.85 (m, 3 H), 2.26 (d, J = 7.0 Hz, 0.5 H), 2.40 (d, J = 7.3 Hz,0.5 H), 2.90 (dd, J = 11.8, 6.9 Hz, 05 H), 3.05-3.30 (m, 2 H), 3.43-3.60(m, 1.5 H), 3.77 (t, J = 6.6 Hz, 2 H), 6.66 (s, 1 H), 7.60 (s, 2 H),7.75-7.83 (m, 2 H), 7.83-7.95 (m, 3 H). MS m/z 468 (M + H)+ 295

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2-methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 6.6 Hz, 4 H), 1.38-1.69 (m,4 H), 1.70-1.95 (m, 3 H), 2.28 (t, J = 7.0 Hz, 0.5 H), 2.41 (d, J = 6.7Hz, 0.5 H), 2.61 (s, 3 H), 2.84-2.98 (m, 0.5 H), 3.07-3.21 (m, 1 H),3.21-3.30 (m, 0.5 H), 3.40- 3.67 (m, 2 H), 3.77 (t, J = 6.7 Hz, 2 H),7.22 (s, 1 H), 7.67 (d, J = 8.4 Hz, 1 H), 7.78-7.86 (m, 2 H), 7.87-7.96(m, 2 H), 7.99 (d, J = 8.4 Hz, 1 H), 8.12 (s, 1 H). MS m/z 484 (M + H)+296

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzo[b]thiophen-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.40(d, J = 6.2 Hz, 4 H), 1.24-1.41 (m, 4 H), 1.46-1.71 (m, 3 H), 2.03 (d, J= 6.9 Hz, 1 H), 2.13 (s, 3 H), 2.28 (s, 3 H), 2.67 (br. s., 0.5 H),2.83-2.99 (m, 2 H), 3.19-3.38 (m, 1.5 H), 3.53 (t, J = 6.8 Hz, 2 H),7.44 (d, J = 8.2 Hz, 1 H), 7.53-7.63 (m, 2 H), 7.66-7.81 (m, 4 H). MSm/z 498 (M + H)+ 297

(R)-5-(4-(1H-indazol-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.52-0.75 (m, 4 H), 1.36-1.50 (m, 1 H), 1.50-1.68 (m, 3 H),1.69-1.96 (m, 3 H), 2.27 (t, J = 7.0 Hz, 1 H), 2.91 (dd, J = 11.8, 6.9Hz, 0.5 H), 3.07-3.31 (m, 2 H), 3.44- 3.64 (m, 1.5 H), 3.77 (t, J = 6.5Hz, 2 H), 7.61-7.71 (m, 1 H), 7.73-7.85 (m, 3 H), 7.85-7.94 (m, 2 H),8.16 (s, 2 H), 13.17 (br. s., 1 H). MS m/z 454 (M + H)+ 298

(R)-5-(4-(benzo[b]thiophen-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.58-0.72 (m, 4 H), 1.38-1.69 (m, 4 H), 1.70-1.96 (m, 3 H), 2.29(t, J = 6.9 Hz, 0.5 H), 2.37-2.49 (m, 0.5 H), 2.91 (dd, J = 11.9, 6.9Hz, 0.5 H), 3.08-3.29 (m, 2 H), 3.39-3.63 (m, 1.5 H), 3.78 (t, J = 6.7Hz, 2 H), 7.56 (d, J = 5.5 Hz, 1 H), 7.72- 7.87 (m, 4 H), 7.90-7.98 (m,2 H), 8.14 (d, J = 8.4 Hz, 1 H), 8.29 (s, 1 H). MS m/z 470 (M + H)+ 299

5-(4-(1H-indol-6-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.52-0.73 (m, 4 H), 1.28-1.47 (m, 1 H), 1.61 (br. s., 2 H), 1.78(br. s., 2 H), 2.72 (br. s., 1 H), 3.44 (d, J = 9.1 Hz, 1 H), 3.69- 3.89(m, 2 H), 3.99 (d, J = 7.1 Hz, 2 H), 4.19 (t, J = 8.2 Hz, 1 H),6.35-6.57 (m, 1 H), 7.43 (br. s., 2 H), 7.67 (d, J = 8.1 Hz, 1 H), 7.77(d, J = 9.3 Hz, 3 H), 7.83-7.95 (m, 2 H), 11.21 (br. s., 1 H). MS m/z439 (M + H)+ 300

5-(4-(1H-indazol-4-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.62 (d, J = 5.1 Hz, 4 H), 1.30-1.45 (m, 1 H), 1.56-1.67 (m, 2 H),1.75-1.87 (m, 2 H), 2.65-2.785 (m, 1 H), 3.46 (dd, J = 9.5, 5.5 Hz, 1H), 3.73-3.86 (m, 2 H), 4.00 (d, J = 7.4 Hz, 2 H), 4.20 (t, J = 8.3 Hz,1 H), 7.34 (d, J = 7.0 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.58-7.65(m, 1 H), 7.85 (m, J = 8.2 Hz, 2 H), 7.93 (m, J = 8.2 Hz, 2 H), 8.24 (s,1 H), 13.30 (s, 1 H). MS m/z 440 (M + H)+ 301

(R)-5-(4-(1H-indol-6-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.65 (d, J = 5.9 Hz, 4 H), 1.34-1.51 (m, 1 H), 1.51-1.68 (m, 3 H),1.69-1.95 (m, 3 H), 2.29 (d, J = 6.7 Hz, 1 H), 2.93 (m, 0.5 H),3.07-3.25 (m, 1.5 H), 3.41-3.66 (m, 2 H), 3.78 (t, J = 6.8 Hz, 2 H),6.48 (d, J = 2.7 Hz, 1 H), 7.34-7.48 (m, 2 H), 7.66 (d, J = 8.2 Hz, 1H), 7.71-7.83 (m, 3 H), 7.83-7.93 (m, 2 H), 11.16 (br. s., 1 H). MS m/z453 (M + H)+ 302

(R)-5-(4-(1H-indol-4-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)metyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.56-0.76 (m, 4 H), 1.45 (dd, J = 12.4, 7.6 Hz, 1 H), 1.53-1.70(m, 3 H), 1.71-1.97 (m, 3 H), 2.25-2.38 (m, 1 H), 2.93 (dd, J = 11.8,6.7 Hz, 0.5 H), 3.06-3.28 (m, 1.5 H), 3.44-3.67 (m, 2 H), 3.79 (t, J =7.1 Hz, 2 H), 7.34 (d, J = 7.0 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.62(d, J = 8.2 Hz, 1 H), 7.81-7.98 (m, 4 H), 8.25 (d, J = 2.5 Hz, 1 H),13.26 (br. s., 1 H). MS m/z 454 (M + H)+ 303

5-(4-(1H-indol-6-yl)-2-methylphenyl)-6-((1-(cyclopropancarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.53-0.70 (m, 4 H), 1.37 (t, J = 6.2 Hz, 1 H), 1.53-1.64 (m, 2 H),1.73-1.84 (m, 2 H), 2.54-2.73 (m, 1 H), 3.33-3.44 (m, 1 H), 3.64-3.82(m, 4 H), 4.17 (t, J = 8.2 Hz, 1 H), 6.48 (br. s., 1 H), 7.35-7.45 (m, 2H), 7.53 (d, J = 7.8 Hz, 1 H), 7.66 (dd, J = 8.0, 5.2 Hz, 2 H), 7.73 (s,2 H), 11.20 (br. s., 1 H). MS m/z 453 (M + H)+ 304

5-(4-(1H-indazol-4-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.60 (d, J = 3.3 Hz, 4 H), 1.37 (quin, J = 6.3 Hz, 1 H), 1.56-1.67(m, 2 H), 1.74-1.85 (m, 2 H), 2.39 (s, 3 H), 2.55-2.74 (m, 1 H), 3.38(dd, J = 9.5, 5.5 Hz, 1 H), 3.64- 3.85 (m, 4 H), 4.18 (t, J = 8.4 Hz, 1H), 7.32 (d, J = 7.0 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 1 H), 7.56-7.66 (m,2 H), 7.68-7.76 (m, 1 H), 7.78 (s, 1 H), 8.25 (s, 1 H), 13.28 (br. s., 1H). MS m/z 454 (M + H)+ 305

(R)-5-(4-(1H-indol-6-yl)-2-methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.51-0.74 (m, 4 H), 1.36-1.65 (m, 4 H), 1.69-1.94 (m, 3 H),2.16-2.36 (m, 1 H), 2.38 (s, 3 H), 2.88 (dd, J = 11.9, 6.5 Hz, 0.5 H),3.05-3.28 (m, 2 H), 3.41-3.64 (m, 3.5 H), 6.48 (d, J = 2.9 Hz, 1 H),7.34- 7.46 (m, 2 H), 7.53 (dd, J = 13.3, 8.0 Hz, 1 H), 7.65 (d, J = 8.2Hz, 2 H), 7.73 (s, 2 H), 11.19 (br. s., 1 H). MS m/z 467 (M + H)+ 306

(R)-5-(4-(1H-indazol-4-yl)-2- methylphenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.65 (d, J = 6.5 Hz, 4 H), 1.36-1.52 (m, 1 H), 1.52-1.66 (m, 3 H),1.70-1.95 (m, 3 H), 2.27 (br. s., 1 H), 2.41 (s, 3 H), 2.88 (dd, J =11.8, 6.4 Hz, 0.5 H), 3.07-3.21 (m, 2 H), 3.44-3.54 (m, 2.5 H), 3.56-3.65 (m, 1 H), 7.32 (d, J = 7.0 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 1 H),7.55-7.67 (m, 2 H), 7.67-7.74 (m, 1 H), 7.76 (br. s., 1 H), 8.25 (s, 1H), 13.24 (br. s., 1 H). MS m/z 468 (M + H)+ 307

(R)-5-(4-(benzo[d]oxazol-2-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.63 (d, J = 5.1 Hz, 4 H), 1.36-1.68 (m, 4 H), 1.69-1.94 (m, 3 H),2.16-2.44 (m, 1 H), 2.88 (dd, J = 11.7, 6.9 Hz, 0.5 H), 3.07- 3.31 (m, 2H), 3.35-3.65 (m, 1.5 H), 3.77 (dd, J = 7.1, 3.6 Hz, 2 H), 7.39-7.56 (m,2 H), 7.78-7.91 (m, 2 H), 7.97 (dd, J = 8.2, 4.3 Hz, 2 H), 8.36 (dd, J =8.2, 1.8 Hz, 2 H). MS m/z 455 (M + H)+ 308

(R)-5-(4-(benzo[d]thiazol-2-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.64 (d, J = 6.5 Hz, 4 H), 1.37-1.67 (m, 4 H), 1.69-1.96 (m, 3 H),2.19-2.33 (m, 1 H), 2.90 (dd, J = 11.8, 6.9 Hz, 0.5 H),k 3.05- 3.32 (m,2 H), 3.36-3.64 (m, 1.5 H), 3.69-3.85 (m, 2 H),k 7.52 (t, J = 7.4 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1 H), 7.93 (dd, J = 8.2, 4.6 Hz, 2 H), 8.12 (d,J = 8.0 Hz, 1 H), 8.21 (d, J = 7.8 Hz, 1 H), 8.24-8.34 (m, 2 H). MS m/z471 (M + H)+ 309

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(quinolin-7-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d,J = 6.3 Hz, 4 H), 1.38-1.68 (m, 4 H), 1.70-1.98 (m, 3 H),k 2.21-2.35 (m,0.5 H), 2.35-2.48 (m, 0.5 H), 2.91 (dd, J = 11.8, 6.9 Hz, 0.5 H),3.07-3.32 (m, 2 H), 3.44-3.64 (m, 1.5 H), 3.78 (t, J = 6.8 Hz, 2 H),7.58 (dd, J = 8.2, 4.1 Hz, 1 H), 7.88 (dd, J = 8.2, 4.6 Hz, 2 H),8.01-8.10 (m, 3 H), 8.10-8.18 (m, 1 H), 8.39 (s, 1 H), 8.44 (d, J = 8.0Hz, 1 H), 8.98 (dd, J = 4.1, 1.4 Hz, 1 H). MS m/z 465 (M + H)+ 310

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(quinolin-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.75(m, 4 H), 1.34-1.56 (m, 1 H), 1.56-1.68 (m, 3 H), 1.73-1.98 (m, 3 H),2.33 (dt, J = 14.2, 7.2 Hz, 1 H), 2.91 (dd, J = 11.9, 6.8 Hz, 0.5 H),3.09-3.32 (m, 2 H), 3.47-3.67 (m, 1.5 H), 3.73-3.86 (m, 2 H), 7.56 (dd,J = 8.5, 4.0 Hz, 1 H), 7.60- 7.72 (m, 3 H), 7.88 (dt, J = 7.9, 3.9 Hz, 3H), 8.12 (d, J = 8.4 Hz, 1 H), 8.23 (t, J = 9.2 Hz, 1 H), 8.98 (d, J =2.9 Hz, 1 H). MS m/z 465 (M + H)+ 311

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(6-fluoronaphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.55-0.74 (m, 4 H), 1.35-1.66 (m, 4 H), 1.70-1.96 (m, 3 H),2.21-2.45 (m, 1 H), 2.90 (dd, J = 11.8, 7.0 Hz, 0.5 H), 3.07- 3.32 (m, 2H), 3.42-3.64 (m, 1.5 H), 3.78 (t, J = 6.5 Hz, 2 H), 7.50 (td, J = 8.9,2.5 Hz, 1 H), 7.78 (dd, J = 10.2, 2.3 Hz, 1 H), 7.86 (dd, J = 8.2, 4.1Hz, 2 H), 7.95-8.09 (m, 4 H), 8.14 (dd, J = 9.1, 5.9 Hz, 1 H), 8.42 (s,1 H). MS m/z 482 (M + H)+ 312

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(quinazolin-7-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.64-0.80 (m, 2 H), 0.86-1.07 (m, 2 H), 1.48-1.58 (m, 1 H), 1.69-1.85(m, 3 H), 1.86-1.97 (m, 2.5 H), 1.97-2.11 (m, 0.5 H), 2.37-2.70 (m, 1H), 3.07 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.24-3.42 (m, 1 H), 3.51-3.91(m, 4.5 H), 7.74-7.84 (m, 2 H), 7.87-7.96 (m, 2 H), 7.99 (dd, J = 8.5,1.4 Hz, 1 H), 8.09 (d, J = 8.4 Hz, 1 H), 8.33 (s, 1 H), 9.41 (s, 1 H),9.48 (s, 1 H). MS m/z 466 (M + H)+ 313

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(8-fluoronaphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.56-0.67 (m, 2 H), 0.87 (dt, J = 7.4, 3.7 Hz, 2 H),1.35-1.47 (m, 1 H), 1.55- 1.75 (m, 3 H), 1.78-1.97 (m, 3 H), 2.28- 2.56(m, 1 H), 2.99 (dd, J = 12.0, 7.0 Hz, 0.5 H), 3.13-3.31 (m, 1 H),3.42-3.82 (m, 4.5 H), 7.13 (dd, J = 10.2, 7.9 Hz, 1 H), 7.31-7.42 (m, 1H), 7.55-7.70 (m, 3 H), 7.75 (dd, J = 8.6, 1.4 Hz, 1 H), 7.82 (dd, J =8.2, 4.5 Hz, 2 H), 7.90 (d, J = 8.5 Hz, 1 H), 8.28 (s, 1 H). MS m/z 482(M + H)+ 314

(R)-5-(4-(1H-indol-3-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.63 (dd, J = 7.7, 3.0 Hz, 2 H), 0.77- 0.95 (m, 2H), 1.38-1.48 (m, 1 H), 1.60- 1.73 (m, 3 H), 1.75-1.99 (m, 3 H), 2.29-2.59 (m, 1 H), 3.01 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.14-3.31 (m, 1 H),3.43-3.65 (m, 2.5 H), 3.66-3.85 (m, 2 H), 7.12- 7.27 (m, 2 H), 7.38 (dd,J = 7.3, 1.9 Hz, 2 H), 7.58 (dd, J = 8.1, 4.5 Hz, 2 H), 7.68- 7.80 (m, 2H), 7.88 (dd, J = 7.7 Hz, 1 H), 8.59 (br. s., 1 H). MS m/z 453 (M + H)+315

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(8-fluoroquinolin-7-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.72 (dd, J = 7.9, 3.1 Hz, 2 H), 0.92 (quin, J = 3.6Hz, 2 H), 1.27-1.39 (m, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.96 (m, 2 H),2.81-2.98 (m, 1 H), 3.66 (dd, J = 9.9, 5.6 Hz, 1 H), 3.94-4.18 (m, 4 H),4.27 (t, J = 8.2 Hz, 1 H), 7.55 (dd, J = 8.4, 4.3 Hz, 1 H), 7.63-7.72(m, 1 H), 7.75 (d, J = 8.4 Hz, 3 H), 7.89 (d, J = 7.3 Hz, 2 H), 8.26 (d,J = 8.4 Hz, 1 H), 9.06 (dd, J = 4.1, 1.4 Hz, 1 H). MS m/z 469 (M + H)+316

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-methyl-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.67-0.82 (m, 2 H), 0.87-1.06 (m, 2H), 1.44-1.57 (m, 1 H), 1.65 (dd, J = 12.6, 7.6 Hz, 0.5 H), 1.75-1.83(m, 2.5 H), 1.84-1.91 (m, 2 H), 1.99 (dd, J = 12.4, 6.3 Hz, 1 H), 2.42(s, 3 H), 2.53 (d, J = 8.2 Hz, 1 H), 2.99-3.04 (m, 0.5 H), 3.15- 3.38(m, 1 H), 3.46-3.69 (m, 4.5 H), 3.99 (s, 3 H), 7.38-7.45 (m, 1 H),7.55-7.67 (m, 6 H), 7.69 (s, 1 H), 7.83 (s, 1 H). MS m/z 508 (M + H)+317

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(2-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300MHz, CHLOROFORM-d) δ ppm 0.64-0.79 (m, 2 H), 0.89-1.04 (m, 2 H),1.43-1.57 (m, 1 H), 1.66 (br. s., 1 H), 1.74-1.83 (m, 2.5 H), 1.83-1.91(m, 2.5 H), 1.95-2.05 (m, 1 H), 2.41 (s, 3 H), 2.49 (s, 3 H), 3.04 (dd,J = 12.0, 6.5 Hz, 0.5 H), 3.14-3.20 (m, 0.5 H), 3.24-3.38 (m, 0.5 H),3.48-3.71 (m, 4.5 H), 6.29 (s, 1 H), 7.34-7.45 (m, 3 H), 7.54-7.65 (m, 2H), 7.78 (s, 1 H), 8.10 (br. s., 1 H). MS m/z 481 (M + H)+ 318

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluoro-[1,1′-biphenyl]-3- yl)cyclopropanesulfonamide ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.65-0.80 (m, 2 H), 0.88-0.98 (m, 2 H),1.01 (d, J = 7.7 Hz, 2 H), 1.18-1.29 (m, 2 H), 1.42-1.58 (m, 1.5 H),1.65- 1.69 (m, 1 H), 1.77-1.87 (m, 2 H), 1.88- 1.97 (m, 2 H), 1.97-2.11(m, 0.5 H), 2.35- 2.49 (m, 1 H), 2.49-2.65 (m, 1 H), 2.92- 3.01 (m, 0.5H), 3.19-3.39 (m, 1 H), 2.44-2.78 (m, 4.5 H), 6.99 (br. s., 1 H), 7.33(d, J = 7.1 Hz, 1 H), 7.37-7.49 (m, 3 H), 7.49-7.59 (m, 2 H), 7.59-7.68(m, 1 H). MS m/z 551 (M + H)+ 319

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.86-1.03 (m, 2 H), 1.46-1.57(m, 1 H), 1.57-1.74 (m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.92 (m, 2 H),1.92-2.08 (m, 1 H), 2.50 (s, 3 H), 2.51-2.65 (m, 1 H), 3.03 (dd, J =12.1, 7.0 Hz, 0.5 H), 3.16-3.37 (m, 1 H), 3.51- 3.79 (m, 4.5 H), 6.31(s, 1 H), 7.38 (s, 2 H), 7.50 (dd, J = 11.2, 6.3 Hz, 1 H), 7.54- 7.64(m, 2 H), 7.78 (s, 1 H), 8.15 (br. s., 1 H). MS m/z 485 (M + H)+ 320

5-(4-(6-chloronaphthalen-2-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.64-0.76 (m, 2 H), 0.86-0.97 (m, 2 H), 1.26-1.37(m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.97 (m, 2 H), 2.81-2.98 (m, 1 H),3.58 (dd, J = 9.9, 5.6 Hz, 1 H), 3.75- 3.87 (m, 1 H), 3.90-4.06 (m, 3H), 4.27 (t, J = 8.3 Hz, 1 H), 7.52 (dd, J = 8.7, 2.0 Hz, 1 H),7.56-7.63 (m, 1 H), 7.65-7.72 (m, 2 H), 7.78 (dd, J = 8.7, 1.8 Hz, 1 H),7.84-7.94 (m, 3 H), 8.09 (s, 1 H). MS m/z 502 (M + H)+ 321

5-(4-(6-chloronaphthalen-2-yl)-2- methylphenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.39-0.48 (m, 2 H), 0.93-1.02 (m, 2 H), 1.19 (s, 3H), 1.76-1.85 (m, 2 H), 1.85-1.94 (m, 2 H), 2.45 (s, 3 H), 2.68- 2.86(m, 1 H), 3.76 (d, J = 7.4 Hz, 4 H), 4.13 (br. s., 2 H), 7.41-7.53 (m, 2H), 7.65-7.73 (m, 2 H), 7.76-7.83 (m, 1 H), 7.83-7.93 (m, 3 H), 8.07 (s,1 H). MS m/z 512 (M + H)+ 322

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.75 (m, 2 H), 0.87-0.98 (m, 2H), 1.25-1.37 (m, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.95 (m, 2 H),2.78-2.97 (m, 1 H), 3.58 (dd, J = 9.8, 5.6 Hz, 1 H), 3.72- 3.86 (m, 1H), 3.88-4.05 (m, 6 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz,1 H), 7.54-7.68 (m, 6 H), 7.70 (s, 1 H), 7.84 (s, 1 H). MS m/z 498 (M +H)+ 323

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.78 (m, 2 H), 0.86-1.02 (m, 2H), 1.40-1.65 (m, 2 H), 1.76-1.86 (m, 2 H), 1.86-1.93 (m, 2 H),1.93-2.10 (m, 1 H), 2.37-2.65 (m, 1 H), 2.99 (dd, J = 12.0, 7.1 Hz, 0.5H), 3.17-3.38 (m, 1 H), 3.47-3.65 (m, 2.5 H), 3.65-3.79 (m, 2 H),3.95-4.06 (m, 3 H), 7.44-7.52 (m, 1 H), 7.53-7.68 (m, 6 H), 7.70 (s, 1H), 7.84 (s, 1 H). MS m/z 512 (M + H)+ 324

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(7-fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.65-0.74 (m, 2 H), 0.86-0.96 (m, 2 H),1.26-1.37 (m, 1 H), 1.77-1.87 (m, 2 H), 1.92 (quin, J = 3.7 Hz, 2 H),2.78- 2.98 (m, 1 H), 3.60 (dd, J = 9.9, 5.6 Hz, 1 H), 3.76-3.89 (m, 1H), 3.90-4.06 (m, 3 H), 4.27 (t, J = 8.3 Hz, 1 H), 7.24 (dd, J = 10.5,7.8 Hz, 12 H), 7.49 (td, J = 7.9, 5.4 Hz, 1 H), 7.58-7.76 (m, 4 H), 7.81(dd, J = 8.7, 1.6 Hz, 1 H), 8.01 (d, J = 8.7 Hz, 1 H), 8.37 (s, 1 H). MSm/z 486 (M + H)+ 325

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4′-(1-isopropyl-1H-pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.47 (dd, J = 7.2, 3.6 Hz, 2 H),0.62- 0.74 (m, 2 H), 1.05 (td, J = 7.7, 3.4 Hz, 1 H), 1.31-1.42 (m, 6H), 1.51-1.60 (m, 2 H), 1.61-1.70 (m, 2 H), 2.19 (s, 3 H), 2.44-2.62 (m,1 H), 3.22-3.37 (m, 1 H), 3.41-3.52 (m, 1 H), 3.53-3.68 (m, 2 H), 3.73(t, J = 9.1 Hz, 1 H), 3.99 (t, J = 8.2 Hz, 1 H), 4.34 (dt, J = 13.4, 6.7Hz, 1 H), 7.18 (d, J = 7.8 Hz, 1 H), 7.29-7.47 (m, 6 H), 7.52 (s, 1 H),7.62 (s, 1 H). MS m/z 522 (M + H)+ 326

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4′-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δppm 0.70 (dd, J = 7.4, 3.8 Hz, 2 H), 0.86- 0.95 (m, 2 H), 1.03-1.13 (m,2 H), 1.13- 1.27 (m, 2 H), 1.27-1.35 (m, 1 H), 1.75- 1.83 (m, m2 H),1.83-1.92 (m, 2 H), 2.42 (s, 3 H), 2.68-2.85 (m, 1 H), 3.54 (dd, J =10.9, 6.3 Hz, 1 H), 3.62-3.75 (m, 2 H), 3.77-3.91 (m, 2 H), 3.96 (t, J =9.1 Hz, 1 H), 4.22 (t, J = 8.3 Hz, 1 H), 7.41 (d, J = 8.0 Hz, 1 H),7.54-7.68 (m, 6 H), 7.78 (s, 1 H), 7.82 (s, 1 H). MS m/z 520 (M + H)+327

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(3-fluoro-4′-(1-isopropyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.4, 3.7 Hz, 2 H),0.87- 0.97 (m, 2 H), 1.30 (td, J = 8.2, 3.9 Hz, 1 H), 1.60 (d, J = 6.7Hz, 6 H), 1.76-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.77-2.97 (m, 1 H),3.58 (dd, J = 9.7, 5.6 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H), 3.88-4.06(m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 4.58 (dt, J = 13.4, 6.7 Hz, 1 H),7.49 (d, J = 11.7 Hz, 1 H), 7.54-7.70 (m, 6 H), 7.76 (s, 1 H), 7.86 (s,1 H). MS m/z 526 (M + H)+ 328

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4′-(1-cyclopropyl-1H-pyrazol-4-yl)-3-fluoro-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.65-0.75 (m, 2 H), 0.87-0.97 (m, 2 H), 1.04-1.14 (m, 2 H), 1.17-1.24(m, 2 H), 1.30 (td, J = 8.2, 4.0 Hz, 1 H), 1.77- 1.86 (m, 2 H),1.86-1.95 (m, 2 H), 2.79- 2.97 (m, 1 H), 3.58 (dd, J = 9.7, 5.7 Hz, 1H), 3.68 (dt, J = 7.3, 3.5 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H),3.88-4.06 (m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1H), 7.55-7.69 (m, 6 H), 7.79 (s, 1 H), 7.82 (s, 1 H). MS m/z 524 (M +H)+ 329

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3-fluoro-[1,1′-biphenyl]-4-yl)-6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.70 (dt, J = 7.2, 3.7 Hz, 2 H), 0.86- 0.98 (m, 2H), 1.30 (dq, J = 8.3, 4.0 Hz, 1 H), 1.77-1.85 (m, 2 H), 1.85-2.04 (m, 4H), 2.47-2.72 (m, 4 H), 2.79-2.96 (m, 1 H), 3.58 (dd, J = 9.7, 5.7 Hz, 1H), 3.74- 3.86 (m, 1 H), 3.88-4.07 (m, 3 H), 4.26 (t, J = 8.2 Hz, 1 H),4.84 (quin, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1 H), 7.55-7.69 (m,6 H), 7.78 (s, 1 H), 7.87 (s, 1 H). MS m/z 538 (M + H)+ 330

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.3, 3.7 Hz, 2 H), 0.91 (t, J = 3.5Hz, 2 H), 1.26-1.34 (m, 1 H), 1.75- 1.83 (m, 2 H), 1.83-2.01 (m, 4 H),2.42 (s, 3 H), 2.48-2.68 (m, 4 H), 2.68-2.85 (m, 1 H), 3.52-3.60 (m, 1H), 3.64-3.76 (m, 1 H), 3.77-3.92 (m, 2 H), 3.96 (t, J = 9.1 Hz, 1 H),4.22 (t, J = 8.2 Hz, 1 H), 4.83 (t, J = 8.3 Hz, 1 H), 7.41 (d, J = 8.1Hz, 1 H), 7.52-7.70 (m, 6 H), 7.77 (s, 1 H), 7.87 (s, 1 H). MS m/z 534(M + H)+ 331

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4′-(1-isopropyl-1H-pyrazol-4-yl-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.56-0.66 (m, 2 H), 0.79-0.87 (m, 2 H),1.19-1.26 (m, 1 H), 1.49 (s, 3 H), 1.51 (s, 3 H), 1.66-1.75 (m, 2 H),1.75- 1.84 (m, 2 H), 2.70-2.83 (m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1H), 3.82-4.06 (m, 4 H), 4.15 (t, J = 8.3 Hz, 1 H), 4.48 (quin, J = 6.7Hz, 1 H), 7.49-7.61 (m, 6 H), 7.64- 7.73 (m, 3 H), 7.77 (s, 1 H). MS m/z508 (M + H)+ 332

5-(4-(6-methoxynaphthalen-2-yl)-2- methylphenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.16-0.32 (m, 2 H), 0.74-0.83 (m, 2 H), 1.00 (s, 3H), 1.55-1.65 (m, 2 H), 1.65-1.77 (m, 2 H), 2.25 (s, 3 H), 2.58 (d, J =7.7 Hz, 1 H), 3.30-3.69 (m, 4 H), 3.79 (s, 3 H), 3.94 (br. s., 2 H),6.97- 7.07 (m, 2 H), 7.25 (d, J = 7.8 Hz, 1 H), 7.46-7.58 (m, 3 H), 7.66(t, J = 8.0 Hz, 2 H), 7.84 (s, 1 H). MS m/z 508 (M + H)+ 333

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(3-methyl-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.54-0.67 (m, 2 H), 0.76-0.86 (m, 2H), 1.20 (td, J = 8.0, 4.4 Hz, 1 H), 1.65- 1.73 (m, 2 H), 1.75-1.82 (m,2 H), 2.32 (s, 3 H), 2.60-2.75 (m, 1 H), 3.42-3.49 (m, 1 H), 3.54-3.66(m, 1 H), 3.67-3.88 (m, 3 H), 3.89 (s, 3 H), 4.13 (t, J = 8.3 Hz, 1 H),7.31 (d, J = 8.0 Hz, 1 H), 7.49 (d, J = 8.1 Hz, 4 H), 7.55 (d, J = 8.4Hz, 2 H), 7.60 (s, 1 H), 7.74 (s, 1 H). MS m/z 494 (M + H)+ 334

5-(2-methyl-4-(6-methylnaphthalen-2- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.22-0.32 (m, 2 H), 0.76-0.87 (m, 2 H), 1.02 (s, 3H), 1.59-1.68 (m, 2 H), 1.68-1.77 (m, 2 H), 2.28 (s, 3 H), 2.40 (s, 3H), 2.50-2.67 (m, 1 H), 3.60 (d, J = 7.4 Hz, 4 H), 3.97 (br. s., 2 H),7.19- 7.32 (m, 2 H), 7.48-7.60 (m, 4 H), 7.63- 7.75 (m, 2 H), 7.89 (s, 1H). MS m/z 492 (M + H)+ 335

5-(2-methyl-4-(1-methyl-1H-indazol-6- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.29-0.40 (m, 2 H), 0.83-0.93 (m, 2 H), 1.10 (s, 3H), 1.65-1.74 (m, 2 H), 1.75-1.84 (m, 2 H), 2.35 (s, 3 H), 2.67 (br. s.,1 H), 3.54 (br. s., 1 H), 3.66 (t, J = 7.3 Hz, 4 H), 4.07 (s, 5 H), 7.34(t, J = 7.8 Hz, 2 H), 7.48-7.60 (m, 3 H), 7.73 (d, J = 8.4 Hz, 1 H),7.94 (s, 1 H). MS m/z 482 (M + H)+ 336

5-(2-methyl-4-(2-methyl-2H-indazol-6- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.37-0.49 (m, 2 H), 0.92-1.02 (m, 2 H), 1.19 (s, 3H), 1.75-1.83 (m, 2 H), 1.83-1.92 (m, 2 H), 2.43 (s, 3 H), 2.68- 2.83(m, 1 H), 3.76 (d, J = 7.6 Hz, 4 H), 4.13 (br. s., 2 H), 4.27 (s, 3 H),7.33- 7.47 (m, 2 H), 7.60-7.69 (m, 2 H), 7.76 (d, J = 8.8 Hz, 1 H), 7.94(d, J = 6.9 Hz, 2 H). MS m/z 482 (M + H)+ 337

5-(4′-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.22-0.32 (m, 2 H), 0.77-0.85 (m, 2 H), 0.87-0.96(m, 2 H), 0.99-1.10 (m, 5 H), 1.58-1.67 (m, 2 H), 1.68-1.75 (m, 2 H),2.26 (s, 3 H), 2.49-2.68 (m, 1 H), 3.38-3.73 (m, 5 H), 3.96 (br. s., 2H), 7.25 (d, J = 8.0 Hz, 1 H), 7.45 (q, J = 8.3 Hz, 6 H), 7.62 (s, 1 H),7.66 (s, 1 H). MS m/z 534 (M + H)+ 338

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.29-0.38 (m, 2 H), 0.84-0.91 (m, 2 H), 1.09 (s, 3H), 1.64-1.73 (m, 2 H), 1.78 (t, J = 3.4 Hz, 2 H), 1.79-1.90 (m, 2 H),2.32 (s, 3 H), 2.38-2.58 (m, 4 H), 2.58-2.71 (m, 1 H), 3.53 (d, J = 6.7Hz, 1 H), 3.65 (d, J = 7.4 Hz, 4 H), 4.02 (br. s., 2 H), 4.74 (quin, J =8.4 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.44-7.59 (m, 6 H), 7.68 (s, 1H), 7.77 (s, 1 H). MS m/z 548 (M + H)+ 339

5-(4-(3-chloroquinolin-7-yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62-0.75 (m, 2 H), 0.86-0.97 (m, 2 H), 1.30 (td, J= 8.2, 4.1 Hz, 1 H), 1.76- 1.85 (m, 2 H), 1.86-1.95 (m, 2 H), 2.77- 2.96(m, 1 H), 3.63 (dd, J = 9.9, 5.5 Hz, 1 H), 3.90-4.06 (m, 3 H), 4.06-4.17(m, 1 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 2 H),7.86-7.97 (m, 4 H), 8.21 (d, J = 2.3 Hz, 1 H), 8.38 (s, 1 H), 8.89 (d, J= 2.5 Hz, 1 H). MS m/z 485 (M + H)+ 340

5-(4-(3-chloroquinolin-7-yl)-2- methylphenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.29-0.39 (m, 2 H), 0.84-0.92 (m, 2 H), 1.10 (s, 3H), 1.72 (t, J = 3.5 Hz, 2 H), 1.75-1.84 (m, 2 H), 2.36 (s, 3 H),2.60-2.74 (m, 1 H), 3.67 (d, J = 7.4 Hz, 4 H), 4.06 (dt, J = 14.4, 7.3Hz, 2 H), 7.40 (d, J = 7.7 Hz, 1 H), 7.58-7.68 (m, 2 H), 7.79 (s, 2 H),8.11 (d, J = 2.1 Hz, 1 H), 8.27 (s, 1 H), 8.80 (d, J = 2.3 Hz, 1 H). MSm/z 513 (M + H)+ 341

(R)-5-(5-(1H-indol-5-yl)pyridin-2-yl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.18-0.34 (m, 2 H), 0.44 (d, J = 4.3 Hz, 2 H),1.03-1.30 (m, 2 H), 1.30-1.37 (m, 2 H), 1.39-1.48 (m, 2 H), 1.61 (m, J =19.0, 12.5, 6.4, 6.4 Hz, 1 H), 2.22- 2.39 (m, 0.5 H), 2.39-2.52 (m, 0.5H), 2.72-2.83 (m, 0.5 H), 2.89-3.02 (m, 1 H), 3.11-3.25 (m, 1.5 H),3.26-3.43 (m, 1 H), 3.73-4.04 (m, 2 H), 6.13 (br. s., 1 H), 6.80-6.92(m, 1 H), 7.03 (d, J = 8.7 Hz, 1 H), 7.13 (d, J = 8.4 Hz, 1 H), 7.50 (s,1 H), 7.62-7.72 (m, 1 H), 7.72-7.81 (m, 1 H), 8.53 (s, 1 H), 10.35 (br.s., 1 H). MS m/z 454 (M + H)+ 342

(R)-5-(5-(benzo[b]thiophen-5-yl)pyridin-2- yl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.56-0.69 (m, 2 H), 0.82-0.96 (m, 2 H), 1.55-1.73(m, 2 H), 1.73-1.79 (m, 2 H), 1.80-1.86 (m, 2 H), 1.87-2.08 (m, 1 H),2.67 (dt, J = 15.1, 7.4 Hz, 0.5 H), 2.74-2.89 (m, 0.5 H), 3.07-3.23 (m,0.5 H), 3.27-3.38 (m, 1 H), 3.48-3.76 (m, 2.5 H), 4.12 (dd, J = 13.5,8.4 Hz, 1 H), 4.21-4.42 (m, 2 H), 7.37 (d, J = 5.4 Hz, 1 H), 7.48 (d, J= 5.5 Hz, 1 H), 7.55 (d, J = 8.5 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H),7.99- 8.08 (m, 2 H), 8.11-8.21 (m, 1 H), 8.89 (br. s., 1 H). MS m/z 471(M + H)+ 343

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)mehtyl)-5-(4-(1-methyl-1H-benzo[d]imidazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.56-0.65 (m, 2 H), 0.76-0.87 (m, 2 H),1.19-1.26 (m, 1 H), 1.68-1.74 (m, 2 H), 1.75-1.84 (m, 2 H), 2.69-2.86(m, 1 H), 3.55 (dd, J = 9.8, 5.6 Hz, 1 H), 3.83 (s, 3 H), 3.85-4.07 (m,4 H), 4.16 (t, J = 8.3 Hz, 1 H), 7.35-7.47 (m, 1 H), 7.49- 7.63 (m, 3H), 7.74 (d, J = 8.2 Hz, 2 H), 7.86 (s, 1 H), 7.99 (s, 1 H). MS m/z 454(M + H)+ 344

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.53-0.67 (m, 2 H), 0.76-0.88 (m, 2 H), 1.19-1.26(m, 1 H), 1.64-1.74 (m, 2 H), 1.74-1.84 (m, 2 H), 2.66-2.86 (m, 1 H),3.55 (dd, J = 9.8, 5.5 Hz, 1 H), 3.77 (s, 3 H), 3.81-4.07 (m, 4 H), 4.14(t, J = 8.3 Hz, 1 H), 6.49 (d, J = 2.9 Hz, 1 H), 7.04 (d, J = 3.0 Hz, 1H), 7.34 (d, J = 8.5 Hz, 1 H), 7.39-7.49 (m, 1 H), 7.56 (m, J = 8.2 Hz,2 H), 7.73 (m, J = 8.1 Hz, 2 H), 7.82 (s, 1 H). MS m/z 453 (M + H)+ 345

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(quinolin-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70(dd, J = 7.6, 3.2 Hz, 2 H), 0.91 (br. s., 2 H), 1.30 (td, J = 8.0, 3.9Hz, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.97 (m, 2 H), 2.72-2.93 (m, 1 H),3.62 (dd, J = 9.5, 5.6 Hz, 1 H), 3.88-4.17 (m, 4 H), 4.24 (t, J = 8.1Hz, 1 H), 7.49-7.66 (m, 1 H), 7.70- 7.84 (m, 3 H), 7.89 (d, J = 8.0 Hz,1 H), 7.96 (d, J = 8.5 Hz, 1 H), 8.21 (d, J = 8.4 Hz, 1 H), 8.27-8.46(m, 3 H). MS m/z 451 (M + H)+ 346

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(quinolin-7-yl)phenyl)-4,6-diazaqspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.42-0.54 (m, 2 H), 0.69 (dt, J = 7.2, 3.4 Hz, 2 H),1.05-1.12 (m, 1 H), 1.54- 1.65 (m, 2 H), 1.65-1.75 (m, 2 H), 2.61- 2.76(m, 1 H), 3.38 (dd, J = 9.9, 5.6 Hz, 1 H), 3.55-3.68 (m, 1 H), 3.68-3.85(m, 3 H), 4.06 (t, J = 8.3 Hz, 1 H), 7.27 (dd, J = 8./2, 4.3 Hz, 1 H),7.38-7.56 (m, 3 H), 7.57-7.67 (m, 1 H), 7.76 (d, J = 8.5 Hz, 1 H), 8.02(d, J = 8.1 Hz, 1 H), 8.17 (s, 1 H), 8.69-8.86 (m, 1 H). MS m/z 469 (M +H)+ 347

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61(br. s., 2 H), 0.82 (br. s., 2 H), 1.16-1.27 (m, 1 H), 1.73 (br. s., 2H), 1.81 (br. s., 2 H), 2.79 (br. s., 1 H), 3.43- 3.56 (m, 1 H), 3.76(br. s., 1 H), 3.80- 3.97 (m, 3 H), 4.06 (s, 3 H), 4.18 (t, J = 8.1 Hz,1 H), 7.35-7.48 (m, 2 H), 7.48-7.65 (m, 3 H), 7.90 (br. s., 1 H), 7.99(s, 1 H). MS m/z 472 (M + H)+ 348

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-benzo[d]imidazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.3, 3.7 Hz, 2 H), 0.78-0.87 (m, 2 H), 1.21 (td, J = 8.0, 4.0 Hz, 1 H), 1.69-1.77 (m, 2 H),1.77-1.88 (m, 2 H), 2.72-2.87 (m, 1 H), 3.51 (dd, J = 9.8, 5.6 Hz, 1 H),3.68-3.80 (m, 1 H), 3.84 (s, 3 H), 3.85-3.97 (m, 3 H), 4.18 (t, J = 8.4Hz, 1 H), 7.39-7.49 (m, 2 H), 7.49-7.58 (m, 3 H), 7.88 (s, 1 H), 7.908(s, 1 H). MS m/z 472 (M + H)+ 349

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6-fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.56-0.66 (m, 2 H), 0.77-0.87 (m, 2 H),1.19-1.27 (m, 1 H), 1.69-1.77 (m, 2 H), 1.79-1.87 (m, 2 H), 2.74-2.88(m, 1 H), 3.49 (dd, J = 9.9, 5.6 Hz, 1 H), 3.68- 3.79 (m, 1 H),3.82-3.97 (m, 3 H), 4.19 (t, J = 8.4 Hz, 1 H), 7.27 (td, J = 8.7, 2.4Hz, 1 H), 7.40-7.53 (m, 2 H), 7.53-7.64 (m, 2 H), 7.71 (s, 1 H),7.79-7.91 (m, 2 H), 8.02 (s, 1 H). MS m/z 486 (M + H)+ 350

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(8-fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.1, 4.0 Hz, 2 H), 0.77-0.88 (m, 2 H), 1.19-1.26 (m, 1 H), 1.68- 1.78 (m, 2 H), 1.78-1.89 (m, 2H), 2.71- 2.89 (m, 1 H), 3.51 (dd, J = 9.8, 5.6 Hz, 1 H), 3.67-3.80 (m,1 H), 3.80-3.98 (m, 3 H), 4.19 (t, J = 8.3 Hz, 1 H), 7.08-7.17 (m, 1 H),7.40 (td, J = 7.9, 5.6 Hz, 1 H), 7.50- 7.67 (m, 4 H), 7.68-7.76 (m, 1H), 7.92 (d, J = 8.4 Hz, 1 H), 8.28 (s, 1 H). MS m/z 486 (M + H)+ 351

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6-methoxynaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.65 (m, 2 H), 0.78-0.86 (m, 2H), 1.20-1.27 (m, 1 H), 1.68-1.76 (m, 2 H), 1.82 (quin, J = 3.7 Hz, 2H), 2.71- 2.87 (m, 1 H), 3.50 (dd, J = 9.9, 5.6 Hz, 1 H), 3.68-3.79 (m,1 H), 3.80-3.97 (m, 6 H), 4.18 (t, J = 8.3 Hz, 1 H), 7.08-7.17 (m, 2 H),7.46-7.66 (m, 4 H), 7.77 (t, J = 9.1 Hz, 2 H), 7.95 (s, 1 H). MS m/z 498(M + H)+ 352

5-(2-fluoro-4-(2-methylbenzo[b]thiophen- 5-yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM- d) δ ppm 0.44 (br. s., 2 H), 0.99 (br. s., 2 H), 1.20 (s, 3H), 1.82 (br. s., 2 H), 1.90 (br. s., 2 H), 2.65 (s, 3 H), 2.85 (br. s.,1 H), 3.86 (br. s., 4 H), 4.17 (br. s., 2 H), 7.07 (s, 1 H), 7.46-7.58(m, 2 H), 7.58- 7.68 (m, 2 H), 7.83-7.96 (m, 2 H). MS m/z 502 (M + H)+353

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2-methylbenzofuran-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR(300 MHz, DMSO-d₆) δ ppm 0.52-0.73 (m, 4 H), 1.32-1.45 (m, 1 H),1.57-1.69 (m, 2 H), 1.77-1.89 (m, 2 H), 2.59-2.77 (m, 1 H), 3.41 (dd, J= 9.8, 5.8 Hz, 1 H), 3.69-3.90 (m, 4 H), 4.18 (t, J = 8.4 Hz, 1 H), 6.66(s, 1 H), 7.57-7.86 (m, 5 H), 7.97 (s, 1 H). MS m/z 472 (M + H)+ 354

(R)-5-(2-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-6- ((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.59-0.95 (m, 4 H), 1.47 (br. s., 2 H), 1.67-1.75(m, 2 H), 1.77-1.90 (m, 3 H), 2.29-2.43 (m, 1 H), 2.55 (s, 3 H), 2.97(br. s., 1 H), 3.41 (br. s., 2 H), 3.57 (br. s., 2.5 H), 3.71 (br. s.,0.5 H), 6.97 (s, 1 H), 7.36-7.47 (m, 2 H), 7.48-7.58 (m, 2 H), 7.77 (d,J = 8.4 Hz, 1 H), 7.79-7.87 (m, 1 H). MS m/z 518 (M + H)+ 355

(R)-5-(2-fluoro-4-(2-methylbenzofuran-5- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.79 (br. s., 2 H), 0.91-1.05 (m, 1 H), 1.11 (br.s., 1 H), 1.36 (br. s., 2 H), 1.66-1.74 (m, 2 H), 1.76-1.90 (m, 3 H),2.27-2.39 (m, 1 H), 2.95 (br s., 0.5 H), 3.17-3.50 (m, 2 H), 3.57 (br.s., 2.5 H), 3.71 (br. s., 1 H), 6.36 (s, 1 H), 7.33- 7.44 (m, 3 H),7.44-7.56 (m, 2 H), 7.63 (s, 1 H). MS m/z 502 (M + H)+ 356

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2-methylbenzo[d]thiazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.75 (m, 2 H), 0.87-0.96 (m, 2H), 1.26-1.37 (m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.96 (m, 2 H),2.83-2.96 (m, 4 H), 3.60 (dd, J = 9.8, 5.7 Hz, 1 H), 3.85 (d, J = 6.3Hz, 1 H), 3.91-4.06 (m, 3 H), 4.27 (t, J = 8.3 Hz, 1 H), 7.28 (s, 2 H),7.54 (d, J = 11.5 Hz, 1 H), 7.60-7.70 (m, 3 H), 7.96 (d, J = 8.2 Hz, 1H), 8.21 (d, J = 1.4 Hz, 1 H). MS m/z 489 (M + H)+ 357

5-(2-fluoro-4-(1-methyl-1H-indaozl-5- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.24-0.34 (m, 2 H), 0.78-0.89 (m, 2 H), 1.05 (s, 3H), 1.61-1.70 (m, 2 H), 1.70-1.81 (m, 2 H), 2.61-2.78 (m, 1 H), 3.70(br. s., 4 H), 4.00 (br. s., 5 H), 7.31- 7.42 (m, 2 H), 7.42-7.57 (m, 3H), 7.84 (s, 1 H), 7.93 (s, 1 H). MS m/z 486 (M + H)+ 358

5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.40-0.49 (m, 2 H), 0.93-1.03 (m, 2 H), 1.20 (s, 3H), 1.76-1.85 (m, 2 H), 1.86-1.96 (m, 2 H), 2.78-2.92 (m, 1 H),3.81-3.94 (m, 3 H), 4.00 (br. s., 4 H), 4.16 (br. s., 2 H), 7.49 (d, J =11.5 Hz, 1 H), 7.55-7.67 (m, 6 H), 7.71 (s, 1 H), 7.84 (s, 1 H). MS m/z512 (M + H)+ 359

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.24-0.34 (m, 2 H), 0.80-0.88 (m, 2 H), 1.06 (s, 3H), 1.62-1.72 (m, 2 H), 1.72-1.82 (m, 2 H), 2.62-2.80 (m, 1 H), 3.52(br. s., 1 H), 3.57-3.82 (m, 3 H), 4.00 (br. s., 2 H), 7.16-7.26 (m, 1H), 7.34-7.48 (m, 2 H), 7.48-7.57 (m, 2 H), 7.64 (s, 1 H), 7.73-7.85 (m,2 H), 7.95 (s, 1 H). MS m/z 500 (M + H)+ 361

(R)-5-(2-fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.44-0.58 (m, 2 H), 0.80-0.99 (m, 2 H), 1.52-1.73(m, 2 H), 1.78-1.87 (m, 2 H), 1.87-2.03 (m, 3 H), 2.50 (dt, J = 14.6,7.3 Hz, 1 H), 2.96-3.12 (m, 1.5 H), 3.66-3.80 (m, 3.5 H), 4.15 (s, 3 H),7.45-7.56 (m, 2 H), 7.58-7.72 (m, 3 H), 7.99 (s, 1 H), 8.09 (s, 1 H). MSm/z 500 (M + H)+ 362

(R)-5-(3-fluoro-4′-(1-methyl-1H-indaozl-5-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.52 (s, 2 H), 0.76-1.02 (m, 2 H), 1.23-1.28 (m, 3H), 1.48-1.70 (m, 2 H), 1.75-1.87 (m, 2 H), 1.88-2.05 (m, 3 H),2.40-2.59 (m, 1 H), 3.06 (br. s., 1 H), 3.27-3.48 (m, 1 H), 3.69 (br.s., 3 H), 3.97 (s, 3 H), 6.40 (d, J = 1.8 Hz, 1 H), 7.51 (d, J = 11.3Hz, 1 H), 7.55-7.71 (m, 5 H), 7.74 (d, J = 8.2 Hz, 2 H). MS m/z 526 (M +H)+ 363

(R)-5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-methylcyclopropancecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.35-0.46 (m, 2 H), 0.68-0.92 (m, 2 H), 1.09-1.16(m, 3 H), 1.51 (br. s., 1 H), 1.65-1.78 (m, 2 H), 1.78-1.89 (m, 3 H),2.40 (dt, J = 14.5, 7.3 Hz, 1 H), 2.98 (br. s., 1 H), 3.20-3.52 (m, 2.5H), 3.60 (br. s., 2.5 H), 7.20-7.30 (m, 1 H), 7.38- 7.53 (m, 2 H),7.54-7.62 (m, 2 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.78-7.89 (m, 2 H), 8.00(s, 1 H). MS m/z 514 (M + H)+ 364

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.34-0.48 (m, 2 H), 0.70-0.90 (m, 2 H), 1.14 (s, 3H), 1.51 (br. s., 1 H), 1.68- 1.76 (m, 2 H), 1.77-1.90 (m, 3 H), 2.39(dt, J = 14.3, 7.2 Hz, 1 H), 2.98 (br. s., 1 H), 3.40 (br. s., 2.5 H),3.52-3.68 (m, 2.5 H), 3.90 (s, 3 H), 7.39 (d, J = 11.3 Hz, 1 H),7.45-7.59 (m, 6 H), 7.61 (s, 1 H), 7.75 (s, 1 H). MS m/z 526 (M + H)+365

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.83 (d, J = 2.7 Hz, 2 H), 1.19 (br. s., 2 H),1.67-1.77 (m, 2 H), 1.77-1.86 (m, 2 H), 2.68-2.84 (m, 1 H), 3.49-3.66(m, 1 H), 3.80 (br. s., 2 H), 4.00 (br. s., 2 H), 4.36 (br. s., 1 H),7.27 (td, J = 8.8, 2.3 Hz, 1 H), 7.39-7.53 (m, 2 H), 7.54-7.62 (m, 2 H),7.70 (s, 1 H), 7.78-7.90 (m, 2 H), 8.01 (s, 1 H). MS m/z 502 (M + H)+366

5-(2-fluoro-4-(6-methoxynaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.63-0.91 (m, 2 H), 1.65 (br. s., 1 H), 1.72 (br.s., 1 H), 1.81 (br. s., 2 H), 1.96 (br. s., 2 H), 2.73 (br. s., 1 H),3.27- 3.65 (m, 3 H), 3.70-4.09 (m, 6 H), 4.19- 4.58 (m, 1 H), 7.03-7.28(m, 2 H), 7.39- 7.61 (m, 3 H), 7.64 (br. s., 1 H), 7.77 (br. s., 2 H),7.95 (br. s., 1 H). MS m/z 514 (M + H)+ 368

6-((1-(1-cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(naphthalen-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.72 (br. s., 2 H), 0.92 (br. s., 2 H), 1.32 (br.s., 1 H), 1.84 (br. s., 2 H), 1.92 (br. s., 2 H), 2.90 (br. s., 1 H),3.61 (br. s., 1 H), 3.86 (br. s., 1 H), 3.98 (br. s., 3 H), 4.28 (br.s., 1 H), 7.59 (br. s., 5 H), 7.95 (br. s., 4 H), 8.13 (br. s., 1 H). MSm/z 468 (M + H)+ 369

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(oxetan-2-carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 1.75-1.86 (m, 2 H), 1.86-1.97 (m, 2H), 2.69-3.03 (m, 3 H), 3.62-3.74 (m, 1 H), 3.79-3.96 (m, 2 H),4.02-4.16 (m, 2 H), 4.21-4.32 (m, 1 H), 4.47-4.70 (m, 2 H), 5.06-5.20(m, 1 H), 7.36 (td, J = 8.7, 2.5 Hz, 1 H), 7.49-7.63 (m, 2 H), 7.64-7.72 (m, 2 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.88-7.99 (m, 2 H), 8.11 (s, 1H). MS m/z 502 (M + H)+ 370

(R)-5-(2-fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.72-0.85 (m, 2 H), 0.88-1.01 (m, 1 H), 1.05 (br.s., 1 H), 1.46 (br. s., 1.5 H), 1.64-1.76 (m, 2.5 H), 1.76-1.92 (m, 3H), 2.28-2.46 (m, 1 H), 2.96 (br. s., 0.5 H), 3.27 (br. s., 1 H), 3.57(br. s., 3 H), 3.71 (br. s., 1.5 H), 4.05 (s, 3 H), 7.33- 7.46 (m, 2 H),7.47-7.63 (m, 3 H), 7.90 (s, 1 H), 7.98 (s, 1 H). MS m/z 502 (M + H)+371

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-5-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.72-.087 (m, 2 H), 0.91-1.14 (m, 2 H), 1.43 (br.,s., 1 H), 1.67-1.77 (m, 2 H), 1.78-1.89 (m, 3 H), 2.27-2.44 (m, 1 H),2.95 (br. s., 0.5 H), 3.29 (br. s., 2 H), 3.50-3.67 (m, 2.5 H), 3.78(br. s., 1 H), 3.87 (s, 4 H), 6.30 (d, J = 1.6 Hz, 1 H), 7.42 (d, J =11.1 Hz, 1 H), 7.45-7.61 (m, 5 H), 7.64 (d, J = 8.2 Hz, 2 H). MS m/z 528(M + H)+ 372

5-(2-fluoro-4-(naphthalen-2-yl)phenyl)-6- ((1-(1-hydroxycyclopropanecarbbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.82 (br. s., 2 H), 1.13 (br. s., 2 H), 1.72 (br.s., 2 H), 1.81 (br. s., 2 H), 2.61- 2.84 (m, 1 H), 3.07 (br. s., 1 H),3.57 (br. s., 1 H), 3.80 (br. s., 2 H), 3.97 (br. s., 2 H), 4.38 (br.s., 1 H), 7.41-7.72 (m, 6 H), 7.76-7.96 (m, 3 H), 8.02 (s, 1 H). MS m/z484 (M + H)+ 373

6-(3-fluoro-4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.85 (br. s., 2 H), 1.17-1.28 (m, 2 H), 1.69-1.78 (m, 2 H), 1.78-1.88(m, 2 H), 2.77 (br. s., 1 H), 3.57 (br. s., 1 H), 3.71-3.88 (m, 2 H),4.00 (br. s., 2 H), 4.35 (br. s., 1 H), 7.52 (d, J = 10.7 Hz, 1 H),7.56-7.66 (m, 3 H), 7.76-7.84 (m, 1 H), 7.90-8.01 (m, 2 H), 8.06 (s, 1H), 8.22 (s, 1 H). MS m/z 509 (M + H)+ 374

5-(2-fluoro-4-(8-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.83 (d, J = 3.0 Hz, 2 H), 1.14-1.21 (m , 2 H),1.67-1.77 (m, 2 H), 1.77-1.89 (m, 2 H), 2.64-2.68 (m, 2 H), 3.57 (br.s., 1 H), 3.80 (br. s., 2 H), 4.00 (br. s., 2 H), 4.38 (br. s., 1 H),7.15 (dd, J = 10.4, 7.9 Hz, 1 H), 7.40 (td, J = 7.9, 5.4 Hz, 1 H),7.48-7.67 (m, 4 H), 77.2 (dd, J = 8.6, 1.7 Hz, 1 H), 7.90 (s, 1 H), 8.28(s, 1 H). MS m/z 502 (M + H)+ 375

5-(2-fluoro-4-(8-methoxynaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.82 (br. s., 2 H), 1.14 (br. s., 2 H), 1.72 (br.s., 2 H), 1.81 (br. s., 2 H), 2.73 (br. s., 1 H), 2.90 (br. s., 1 H),3.57 (br. s., 1 H), 3.67-3.85 (m, 2 H), 3.85-4.11 (m. 5 H), 4.35 (br.s., 1 H), 6.80 (br. s., 1 H), 7.39 (br. s., 2 H), 7.46-7.59 (m, 2 H),7.59-7.72 (m, 2 H), 7.84 (d, J = 8.4 Hz, 1 H), 8.46 (br. s., 1 H). MSm/z 514 (M + H)+ 377

5-(2-fluoro-4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆)δ ppm 0.39-0.51 (m, 2 H), 0.64-0.75 (m, 2 H), 1.38 (d, J = 3.7 Hz, 2 H),1.57 (d, J = 3.6 Hz, 2 H), 2.34-2.51 (m, 1 H), 3.18 (br. s., 1 H), 3.53(br. s., 3 H), 3.65 (s, 3 H), 3.79 (br. s., 1 H), 4.04-4.21 (m, 1 H),7.40- 7.66 (m, 6 H), 7.87 (s, 1 H), 8.03 (s, 1 H). MS m/z 488 (M + H)⁺378

5-(2-fluoro-4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.29-0.39 (m, 2 H), 0.89 (br. s., 2 H), 1.67-1.76(m, 2 H), 1.77-1.85 (m, 2 H), 2.65-2.83 (m, 1 H), 3.50-3.82 (m, 4 H),3.83 (s, 3 H), 4.06 (br. s., 2 H), 7.37- 7.48 (m, 2 H), 7.48-7.59 (m, 3H), 7.87 (s, 1 H), 7.97 (s, 1 H). MS m/z 486 (M + H)+ 379

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.69-0.85 (m, 2 H), 0.88-0.99 (m, 1 H), 1.03 (br.s., 1 H), 1.28-1.55 (m, 1 H), 1.66-1.76 (m, 2 H), 1.76-1.89 (m, 3 H),2.34 (dt, J = 14.2, 7.1 Hz, 0.5 H), 3.29 (br. s., 2 H), 3.49-3.66 (m,2.5 H), 3.75 (br. s., 1 H), 3.89 (s, 3 H), 3.96-4.17 (m, 1 H), 7.38 (d,J = 11.3 Hz, 1 H), 7.43-7.58 (m, 6 H), 7.60 (s, 1 H), 7.74 (s, 1 H). MSm/z 528 (M + H)+ 380

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(8-methoxynaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.77 (m, 2 H), 0.91 (br. s., 2H), 1.30 (dd, J = 7.8, 3.6 Hz, 1 H), 1.82 (br. s., 2 H), 1.91 (br. s., 2H), 2.78-2.99 (m, 1 H), 3.60 (dd, J = 9.1, 5.6 Hz, 1 H), 3.77- 3.88 (m,1 H), 3.88-4.03 (m, 3 H), 4.07 (s, 3 H), 4.26 (t, J = 8.2 Hz, 1 H), 6.90(d, J = 4.3 Hz, 1 H), 7.41-7.53 (m, 2 H), 7.57- 7.69 (m, 2 H), 7.69-7.81(m, 2 H), 7.93 (d, J = 8.5 Hz, 1 H), 8.55 (s, 1 H). MS m/z 498 (M + H)+381

(R)-5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.00 (br. s., 2 H), 0.11-0.31 (m, 2 H), 0.62-0.76(m, 1 H), 0.86-0.98 *nm m2 H), 0.98-1.11 (m, 3 H), 1.59 (br. s., 1 H),2.22 (br. s., 1 H), 2.48-2.65 (m, 2 H), 2.86 (d, J = 7.3 Hz, 3 H),2.98-3.20 (m, 1 H), 5.03 (br. s., 1 H), 6.57 (td, J = 8.7, 2.3 Hz, 1 H),6.77 (dd, J = 9.8, 2.2 Hz, 1 H), 6.84-7.00 (m, 3 H), 7.02-7.11 (m, 1 H),7.12-7.28 (m, 2 H), 7.43 (s, 1 H). MS m/z 516 (M + H)+ 382

5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.76-0.89 (m, 2 H), 1.14-1.23 (m, 2 H), 1.66-1.76(m, 2 H), 1.76-1.87 (m, 2 H), 2.65-2.77 (m, 1 H), 2.81 (br. s., 1 H),3.58 (br. s., 1 H), 3.78 (br. s., 2 H), 3.90 (s, 3 H), 4.01 (br. s., 2H), 4.36 (br. s., 1 H), 7.39 (d, J = 11.5 Hz, 1 H), 7.45- 7.58 (m, 6 H),7.61 (s, 1 H), 7.75 (s, 1 H). MS m/z 514 (M + H)+ 383

5-(4-(6-chloronaphthalen-2-yl)-2- fluorophenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.76-0.88 (m, 2 H), 1.16 (br. s., 2 H), 1.68-1.77(m, 2 H), 1.78-1.88 (m, 2 H), 2.65-2.87 (m, 2 H), 3.57 (br. s., 1 H),3.80 (br. s., 2 H), 3.98 (br. s., 2 H), 4.36 (br. s., 1 H), 7.37-7.53(m, 2 H), 7.53- 7.63 (m, 2 H), 7.63-7.75 (m, 1 H), 7.75- 7.88 (m, 3 H),7.99 (s, 1 H). MS m/z 518 (M + H)+ 384

5-(2-fluoro-4-(7-fluoronaphthalen-2- yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.82 (br s, 2 H), 1.13 (br s, 2 H), 1.72 (br s, 2H), 1.81 (br s, 2 H), 2.65-2.82 (m, 1 H), 2.95 (br s, 2 H), 3.36-4.58 (m, 6 H), 7.24 (t, J = 8.2 Hz, 1 H), 7.44-7.62 (m, 5 H), 7.80 (t, J = 6.9Hz, 1 H), 7.88 (d, J = 8.3 Hz, 1 H), 7.94 (s, 1 H) MS m/z 502 (M + H)+385

6-(3-fluoro-4-(6-((1-(1- methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.45 (br. s., 2 H), 0.99 (br. s., 2 H), 1.21 (br. s., 3 H), 2.87 (br.s., 1 H), 3.50 (d, J = 6.2 Hz, 1 H), 3.61-4.00 (m, 3 H), 4.17 (br. s., 2H), 7.62 (d, J = 10.7 Hz, 1 H), 7.71 (br. s., 3 H), 7.88 (d, J = 8.0 Hz,1 H), 7.96-8.11 (m, 2 H), 8.15 (br. s., 1 H), 8.31 (br. s., 1 H). MS m/z507 (M + H)+ 387

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 388

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 389

6-{[(3R)-1-(Cyclopropylcarbonyl)piperidin-3-yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 468 (M + H)+ 390

5-[5-(1-Benzofuran-5-yl)pyridin-2-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z (M + H)+ 391

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-methyl-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 392

5-[4-(1-Benzothiophen-5-yl)-3- methylphenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 393

5-[4-(1-Benzofuran-5-yl)-3-methylphenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 394

5-[4-(1-Benzothiophen-5-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)piperidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484 (M + H)+ 395

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)piperidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 396

6-{[(3R)-1-(Cyclopropylcarbonyl)piperidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 397

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1-methyl-1H-indazol-5-yl)pyridin-2-yl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z (M + H)+ 398

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1-benzofuran-5-yl)-2-methylphenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 482 (M + H)+ 399

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(2,3-dimethyl-1- benzofuran-5-yl)-3-fluorophenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 500 (M + H)+ 400

5-[4-(6-Aminopyridin-2-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 401

Methyl 4′-(6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl-3-carboxylate MS m/z 472 (M + H)+ 402

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[6-(1H-indol-5-yl)pyridin-3-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 404

5-[4-(1-Benzothiophen-5-yl)-3- fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 474 (M + H)+ 405

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 406

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(2,3-dimethyl-1-benzothiophen-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 516 (M + H)+ 407

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-5-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 494 (M +H)+ 408

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 430 (M + H)+ 409

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 410

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 411

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 494 (M +H)+ 412

5-(3″-Chloro-1,1′:4′,1″-terphenyl-4-yl)-6-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 524 (M + H)+ 413

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4″-methyl-1,1′:4′,1″-terphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 504 (M + H)+414

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-fluoro-4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 415

5-[4-(1-Benzofuran-5-yl)-3-fluorophenyl]-6-{[(1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 416

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 417

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1-benzofuran-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 486 (M + H)+ 418

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1-benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z484 (M + H)+ 419

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indazol-5-yl)pyridin-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 420

5-[6-(1-Benzofuran-5-yl)pyridin-3-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 455 (M + H)+ 421

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[6-(1-methyl-1H-indazol-5-yl)pyridin-3-yl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 469 (M + H)+422

5-[5-(1-Benzofuran-5-yl)thiophen-2-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 460 (M + H)+ 423

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indol-5-yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 424

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indazol-5-yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 460 (M + H)+ 425

5-[5-(1-Benzothiophen-5-yl)thiophen-2-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 476 (M + H)+ 426

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(3H-indol-6-yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 427

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indazol-4-yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 460 (M + H)+ 428

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indol-6-yl)pyridin-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 429

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1H-indazol-4-yl)pyridin-2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 430

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1-methyl-1H-indazol-5-yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 474 (M +H)+ 431

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 432

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-1-benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z470 (M + H)+ 433

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 488 (M + H)+ 434

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1-benzothiophen-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 502 (M + H)+ 435

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1H-indol-5-yl)-3-methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 453 (M + H)+436

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 468 (M + H)+ 437

5-[5-(1-Benzofuran-5-yl)pyrimidin-2-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 438

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[5-(1-methyl-1H-indazol-5-yl)pyrimidin-2-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 470 (M +H)+ 439

5-[5-(1-Benzofuran-5-yl)pyrazin-2-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 440

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(1H-indol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 457 (M + H)+ 441

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 442

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(1H-indol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 457 (M + H)+ 443

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(1H-indazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 444

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1H-indazol-5-yl)-3-methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 468 (M + H)+445

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1H-indazol-4-yl)-3-methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 468 (M + H)+446

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 447

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1-benzothiophen-5-yl)-3-methylphenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 498 (M + H)+ 448

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1H-indazol-5-yl)-3-methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 454 (M + H)+449

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1H-indazol-6-yl)-3-methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 453 (M + H)+450

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 451

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 452

5-[4-(2-Aminppyridin-4-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 453

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3,4-dihydro-1H-2- benzopyran-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 470 (M + H)+ 454

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 455

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4-quinolin-6-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 465 (M + H)+ 456

6-{[(3R)-1- (Cycloprop-ylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(2,3-dihydro-1,4- benzodioxin-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 457

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1,3-dihydro-2H-indol-2- one MS m/z 469 (M + H)+ 458

5-[2-(1-Benzofuran-5-yl)pyrimidin-5-yl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}0-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 459

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[2-(1-methyl-1H-indazol-5-yl)pyrimidin-5-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 470 (M +H)+ 460

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-2-methylphenyl]-1-benzofuran-2-carbonitrile MS m/z 479 (M + H)+ 461

6-[4-(6-{[(3R)-1- (Cyclopropylcvarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1,3-dihydro-2H-indol-2- one MS m/z 469 (M + H)+ 462

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(2,3-dihydro-1- benzofuran-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 456 (M + H)+ 463

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-2-fluorophenyl]-1-benzofuran- 2-carbonitrile MS m/z 497 (M +H)+ 464

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3,4-dihydro-2H-chromen-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 470 (M + H)+ 465

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3-cyclopropyl-1-methyl- 1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 466

5-[4-(3-Chloroisoquinolin-6-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 467

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]isoquinolin-1(2H)-one MS m/z 481 (M + H)+ 468

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1-methoxyisoquinolin-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 495 (M + H)+ 469

5-[4-(1-Aminoisoquinolin-6-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 480 (M + H)+ 470

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3-methoxyisoquinolin-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 495 (M + H)+  71

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3,4-dihydro-1H-2- benzopyran-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 470 (M + H)+ 471

5-[2-Methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-6-[(1-propanoylazetidin-3-yl)methyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456.3 (M + H)+ 473

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(2-methylpropanoyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 470.3 (M + H)+ 474

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-(4-quinolin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 465 (M + H)+ 475

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1- benzofuran-2-carbonitrile MSm/z 465 (M + H)+ 476

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-2-methylphenyl]-1-benzofuran- 2-carbonitrile MS m/z 493 (M +H)+ 477

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-2-fluorophenyl]-1-benzofu8ran-2-carbonitrile MS m/z 483 (M + H)+ 478

5-[4-(6-Bromoisoquinolin-3-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 479

5-[4-(1-Chloroisoquinolin-6-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 480

6-[(1-{[1- (Hydroxymethyl)cyclopropyl]carbonyl}azetidin-3-yl)methyl]-5-[2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498.3(M + H)+ 481

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-quinoxalin-6-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 452 (M + H)+ 482

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(6-pyrrolidin-1-ylpyridin-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 483

5-[4-(3-Amino-1-methyl-1H-indazol-6- yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 483 (M + H)+ 484

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{4-[3-(methoxymethyl)-1-methyl-1H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 512 (M + H)+ 485

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{4-[3-(hydroxymethyl)-1-methyl-1H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)+ 486

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{4-[3-(methoxymethyl)-2-methyl-2H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 512 (M + H)+ 487

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{4-[3-(hydroxymethyl)-2-methyl-2H-indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)+ 488

N,N-Dimethyl-3-({5-[2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-7-oxo-4,6- diazaspiro[2.4]hept-4-en-6-yl}methyl)azetidine-1-carboxamide[] MS m/z 471.3 (M + H)+ 489

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482.3 (M + H)+

ID No. Structure Compound Name & Physical Data 490

5-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-6-{[(3R)-1-(oxetan-3-ylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484.1 (M + H)+ 491

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,4-dimethyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 492

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,7-dimethyl-1H-indazol-5-yl)phenyl]-4,6-dazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 493

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1-methyl-1H-indazole- 3-carbonitrile MS m/z 493 (M +H)+ 494

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)biphenyl-3-carboxamide MS m/z 457 (M + H)+ 495

6-{[1-(2-Hydroxy-2- methylpropanoyl)azetidin-3-yl]methyl}-5-[2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 486.3 (M + H)+ 496

5-[2-Methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-6-({1-[(3-methyloxetan-3-yl)carbonyl]azetidin-3-yl}methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498.2 (M + H)+ 497

5-[4-(1H-Benzimidazol-2-yl)phenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 498

6-({1-[(1- Hydroxycyclopropyl)carbonyl]-azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484.3 (M + H)+ 499

6-{[1-(Cyclopropylacetyl)azetidin-3-yl]methyl}-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482.3 (M + H)+ 500

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-rn-5-yl)phenyl]-1,2-dimethyl-1,2- dihydro-3H-indazol-3-one MS m/z 498(M + H)+ 501

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[2-(cyclopropylmethyl)-2H- indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 494 (M + H)+ 502

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(3-fluoroisoquinolin-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 469 (M + H)+ 503

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 455 (M + H)+ 504

5-[4-(1,2-Benzisoxazol-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 441 (M + H)+ 505

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-ethyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 506

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-ethyl-2H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 507

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-methyl-2H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 508

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[1-(1-methylethyl)-1H-indol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 481 (M +H)+ 509

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[6-(1H-imidazol-1- yl)pyridin-3-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 467 (M + H)+ 510

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-methylquinolin-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 511

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,8-naphthyridin-2-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 512

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-3,4-dihydroquinolin- 2(1H)-one MS m/z 483 (M + H)+ 513

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-methylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 514

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-5-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 480 (M +H)+ 515

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-indazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 516

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-{6-[1-(1-methylethyl)-1H-pyrazol-4-yl]pyridin-3-yl}phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 509 (M + H)+ 517

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[6-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 518

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]methyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 511.2 (M + H)+ 519

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-quinolin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 451 (M + H)+ 520

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,7-dimethyl-1H-indazol- 5-yl)-2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 521

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-ethyl-1H-indazol-5-yl)-2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 486 (M + H)+522

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-cyclopropyl-1-indazol- 5-yl)-2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 423

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[1-(cyclopropylmethyl)-1H-indazol-5-yl]-2-fluorophenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z512 (M + H)+ 524

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[2-(cyclopropylmethyl)-2H-indazol-5-yl]-2-fluorophenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z512 (M + H)+ 525

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[1-(1-methylethyl)-1H-indol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 499 (M + H)+ 526

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{2-fluoro-4-[6-(1H-imidazol-1- yl)pyridin-3-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 527

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[1-(2-hydroxyethyl)-1H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 528

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(1H-indazol-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 529

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[2-fluoro-4-(1H-indazol-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 530

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[3-(hydroxymethyl)-1-methyl-1H-indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 484 (M + H)+ 531

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-isoquinolin-3-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 451 (M + H)+ 532

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2-hydroxyquinolin-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 467 (M + H)+ 533

3-{5-[4-(6-{[1- (Cyclopropylcarbonyl)azetidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1H-indazol-1- yl}propanenitrile MS m/z 493 (M + H)+534

6-{[1-(Cycloprropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[5-(1-methyl-1H-pyrazol-4- yl)pyridin-2-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 535

5-[4-(4-Chloro-2-methylquinolin-7- yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 536

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[2-(2-hydroxyethyl)-2H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 537

5-(4′-Chloro-2′,3-difluorobiphenyl-4-yl)-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 538

5-[4-(1H-Benzimidazol-2-yl)-2- fluorophenyl]-6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 539

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-[1,2,4]triazolo[4,3- a]pyridin-6-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 441 (M + H)+ 540

5-[4-(2-Chloroquinolin-7-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 485 (M + H)+ 541

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1-methyl-1H-indol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 453 (M + H)+ 542

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-3-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 480 (M +H)+ 543

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-(4-quinazolin-7-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 452 (M + H)+ 544

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4′-[1-(2-methylpropyl)-1H-pyrazol-4-yl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z522 (M + H)+ 545

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(oxetan-2-ylcarbonyl)azetidin-3-yl]methyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 484.2 (M + H)+ 546

6-{[1-(3-Hydroxy-2,2- dimethylpropanoyl)azetidin-3-yl]methyl}-5-[2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 500.3 (M + H)+ 547

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3-fluoro-4′-(1-methyl-1H- pyrazol-3-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 548

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 488 (M + H)+ 549

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[2-(2-hydroxyethyl)-2H- indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 550

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indazol-6-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 551

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indazol-6-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 552

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-fluoro-1-(2-hydroxyethyl)-1H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hep-t-4-en-7-one MS m/z 502 (M + H)+ 553

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-fluoro-2-(2-hydroxyethyl)-2H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 554

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(4-methylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 555

5-[4-(2-Chloro-3-methylquinolin-7- yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 556

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[1-(2-hydroxyethyl)-1H- indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 557

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[4-(3-methoxy-1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 558

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(2-methyl-1,3- benzothiazol-6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 489 (M + H)+ 559

5-[4-(2-Chloro-4-methylquinolin-7- yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 560

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(8-fluoroquinolin-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 469 (M + H)+ 561

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(8-fluoro-2-methylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 562

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-1,3-benzothiazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 471(M + H)+ 563

5-[4-(4-Chloroquinolin-7-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 485 (M + H)+ 564

6-({1-[(1- Aminocyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 483.3 (M + H)+ 566

5-[3-Fluoro-4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 512 (M + H)+ 568

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3-(2-hydroxyethyl)-1-methyl-1H-indol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 515 (M + H)+ 569

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,2-dimethyl-1H-indol-5- yl)-2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 570

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(2,4-dimetrhylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 479 (M + H)+ 571

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl}methyl]-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′- methylbiphenyl-3-yl]cyclopropanecarboxamide MS m/z 497 (M + H)+ 572

5-[2-Fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-({1-[(1-hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 573

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,3-dimethyl-1H-indol-5- yl)-2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 574

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(2-methylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 575

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(2-methylquinolin-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 576

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(2- methylquinolin-7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 577

5-[3-Fluoro-4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-6-({1-[(1-hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 514 (M + H)+ 578

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′- methylbiphenyl-3-yl]cyclopropanesulfonamide MS m/z 533 (M + H)+ 579

7-{3-Methyl-4-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl]phenyl}quinoline-2-carboxamide MS m/z 522 (M + H)+ 580

2-Fluoro-3′-methyl-4′-[6-(]1-{(1- methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl]biphenyl-4-carbonitrile MS m/z 471 (M + H)+ 581

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-{2-methyl-4-[6-(1- methylethoxy)naphthalen-2-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 536 (M + H)+ 582

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(1,2-dimethyl-1H-indol-5- yl)-2-methylphenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 583

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5- yl)phenyl] quinoline-2-carboxylic acid MSm/z 495 (M + H)+ 584

5-[2-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 585

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-fluorobiphenyl-3- yl]cyclopropanecarboxamide MS m/z 515(M + H)+ 586

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[3-(hydroxymethyl)-1-methyl-1H-indazol-5-yl]-2-methylphenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 587

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[3-(hydroxymethyl)-2-methyl-2H-indazol-5-yl]-2-methylphenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 588

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[3-(methoxymethyl)-1-methyl-1H-indazol-5-yl]-2-methylphenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 589

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-{4-[3-(methoxymethyl)-2-methyl-2H-indazol-5-yl]-2-methylphenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 590

5-[4-(3-Chloro-1-methyl-1H-indazol-6-yl)- 2-methylphenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 502 (M + H)+ 591

5-[4-(3-Chloro-1-methyl-1H-indazol-5-yl)- 2-methylphenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 502 (M + H)+ 592

5-[4-(4-Chloro-1H-indazol-6-yl)-2- fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 492 (M + H)+ 593

1-{2-Fluoro-3-methyl-4-[6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]biphenyl-4-yl}cyclopropanecarbonitrile MS m/z 511 (M + H)+ 594

5-[4-(2-Chloroquinolin-7-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 513 (M + H)+ 595

5-[4-(7-Bromoquinolin-2-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 557 (M + H)+ 596

5-[4-(2-CHloro-3-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl)]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 527 (M + H)+ 597

5-[4-(4-Chloro-2-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 527 (M + H)+ 598

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(2-methyl-2H- indazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 599

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 600

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 601

5-{4′-[1-(Cyclopropylmethyl)-1H-pyrazol-3-yl]-3-methylbiphenyl-4-yl}-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 548 (M + H)+ 602

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-{3-methyl-4′-[1-(2-methylpropyl)-1H-pyrazol-3-yl]biphenyl-4-yl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 550 (M + H)+ 603

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(2- methylquinolin-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 604

7-{3-Methyl-4-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl]phenyl}quinoine-2-carbonitrile MS m/z 504 (M + H)+ 605

5-[4-(7-Bromo-4-methylquinolin-2-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 571 (M + H)+ 606

5-[4-(3-Chloro-1-methyl-1H-indazol-6-yl)- 2-fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 506 (M + H)+ 607

5-[4-(3-Chloro-1-methyl-1H-indazol-5-yl)- 2-fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 506 (M + H)+ 608

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3-(methoxymethyl)-1-methyl-01H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 516 (M + H)+ 609

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3-(hydroxymethyl)-1-methyl-1H-indazol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 502 (M + H)+ 610

5-[4-(6-]{1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3- methylphenyl]-2-methyl-2H-indazole-3-carbonitrile MS m/z 493 (M + H)+ 611

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5- yl)phenyl]quinolin-2-carbonitrile MS m/z 476(M + H)+ 612

5-[3-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyk}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 613

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-methylbiphenyl-3- yl]cyclopropanesulfonamide MS m/z 547(M + H)+ 614

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-methylbiphenyl-3- yl]cyclopropanecarboxamide MS m/z 511(M + H)+ 615

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′- fluorobiphenyl-3-yl]cyclopropanecarboxamide MS m/z 501 (M + H)+ 616

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl]naphthalene-2-carbonitrile MS m/z 493 (M + H)+ 617

5-[2-Fluoro-4-(7-methoxynaphthalen-2- yl)phenyl]-6-({1-[(1-hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 514 (M + H)+ 618

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(7-methoxynaphthalen-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)+ 619

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′- fluorobiphenyl-3-yl]cyclopropanesulfonamide MS m/z 537 (M + H)+ 620

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-{2-methyl-4-[2- (trifluoromethyl)quinolin-7-yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 547 (M + H)+ 621

7-{3-Fluoro-4-[6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl]phenyl}naphthalene-2- carbonitrile MS m/z 509 (M + H)+ 622

5-[3-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-({1-[(1-hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 504 (M + H)+ 623

6-({(3R)-1-[(1- Methylcyclopropyl)carbonyl]pyrrolidin-3-yl}methyl)-5-[3-methyl-4′-(1-methyl-1H- pyrazol-5-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 624

5-[4-(2-Chloro-4-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 527 (M + H)+ 627

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- benzimidazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 628

6-({1-[(1- Hydroxycyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-methyl-4-(1-methyl-1H- benzimidazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 629

5-[4-(4-Chloro-1H-indazol-6-yl)-2- methylphenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 630

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2′,3-difluoro-5′-(trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 504 (M + H)+ 631

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{3-fluoro-3′-[(1-methylethyl)sulfonyl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 524 (M + H)+ 632

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{3-fluoro-3′-[(1- methylethyl)sulfonyl]biphenyl-4-yl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 538 (M + H)+ 633

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-methyl-3′- (methylsulfonyl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 506 (M + H)+ 634

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3-fluoro-3′- (methylsulfonyl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z (M + H)+ 635

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(5-methoxynaphthalen-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 498 (M + H)+ 636

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-{3-methyl-3′-[(1- methylethyl)sulfonyl]biphenyl-4-yl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 534 (M + H)+ 637

6-({1-[(1- Fluorocyclopropyl)carbonyl]azetidin-3-yl}methyl)-5-[2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 490,2 (M + H)+ 638

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(5-fluoro-1,3- benzothiazol-2-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 639

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4-(5,6-difluoro-1,3-benzothiazol-2-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 511 (M + H)+ 640

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- methylbiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 518 (M + H)+ 641

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- fluorobiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 504 (M + H)+ 642

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- methylbiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 500 (M + H)+ 643

5-[4-(5-Chloro-1,3-benzothiazol-2-yl)-2- fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 509 (M + H)+ 644

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(2-methyl-2H- indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 472.2 (M + H)+ 645

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- fluorobiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 490 (M + H)+ 646

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- methylbiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 532 (M + H)+ 647

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 536 (M + H)+ 648

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(1-methyl-1H- benzimidazol-2-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 649

5-[4-(6-Chloro-1,3-benzoxazol-2-yl)-2- fluorophenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 493 (M + H)+ 650

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- methylbiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 651

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 652

2-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3- fluorophenyl]-1,3-benzothiazole-5-carbonitrile MS m/z 500 (M + H)+ 653

6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[2-fluoro-4-(6-fluoro-1-methyl-1H-benzimidazol-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 490 (M + H)+ 654

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,2-dimethyl-1H-benzimidazol-6-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 486 (M + H)+ 655

3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm0.67-0.74 (m, 2 H), 0.90-0.97 (m, 2 H), 1.41-1.56 (m, 4 H), 1.56-1.75(m, 2 H), 1.77-1.86 (m, 0.5 H), 1.88-1.99 (m, 0.5 H), 2.07-2.18 (m, 2H), 2.30- 2.39 (m, 0.5 H), 2.41-2.52 (m, 0.5 H), 3.00 (dd, J = 12.1, 7.2Hz, 0.5 H), 3.20 (dd, J = 9.8, 7.9 Hz, 0.5 H), 3.29 (dt, J = 12.1, 7.7Hz, 0.5 H), 3.46-3.55 (m, 1.5 H), 3.56-3.68 (m, 1.5 H), 3.69-3.79 (m,1.5 H), 3.96-3.99 (m, 3 H), 3.99-4.08 (m, 4 H), 7.57-7.61 (m, 2 H),7.61-7.79 (m, 5 H), 7.73-7.79 (m, 2 H), 7.82 (s, 1 H) MS m/z 538.3 (M +H)+ 656

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4- one MS m/z 542.2 (M + H)+ 657

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm1.41-1.61 (m, 4 H), 1.77-1.93 (m, 2 H), 1.93-2.05 (m, 2 H), 2.05-2.20(m, 3 H), 2.32-2.44 (m, 1 H), 3.02 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.08(dd, J = 10.6, 7.2 Hz, 0.5 H), 3.28-3.39 (m, 1 H), 3.45- 3.55 (m, 1 H),3.58-3.68 (m, 1.5 H), 3.68- 3.75 (m, 1.5 H), 3.77-3.84 (m, 1 H), 3.90(quin, J = 7.3 Hz, 1 H), 3.99 (s, 3 H), 4.00-4.08 (m, 4 H), 4.33 (t, J =6.6 Hz, 0.5 H), 4.40 (dd, J = 7.4, 5.9 Hz, 0.5 H), 7.56- 7.61 (m, 2 H),7.61-7.70 (m, 5 H), 7.76 (dd, J = 8.3, 5.3 Hz, 2 H), 7.82 (s, 1 H) MSm/z 568.2 (M + H)+ 658

Methyl (3S)-3-({2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4-oxo-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-3-yl}methyl)pyrrolidin-1-carboxlate MS m/z 528.2 (M + H)+ 659

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-{[(3R)-1-(trifluoroacetyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 566.2 (M +H)+ 660

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm1.38-1.58 (m, 4 H), 1.68-1.84 (m, 5 H), 2.06-2.18 (m, 2 H), 2.25-2.38(m, 1 H), 2.98 (dd, J = 10.5, 7.3 Hz, 1 H), 3.20- 3.29 (m, 6 H), 3.32(dd, J = 10.5, 7.0 Hz, 1 H), 3.67 (dd, J = 14.4, 7.2 Hz, 1 H), 3.73 (dd,J = 14.3, 7.8 Hz, 1 H), 3.98 (s, 3 H), 4.00-4.08 (m, 3 H), 7.59 (m, J =8.3 Hz, 2 H), 7.62-7.70 (m, 5 H), 7.76 (d, J = 8.3 Hz, 2 H), 7.83 (s, 1H) MS m/z 567.3 (M + H)+ 661

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δppm 0.66-0.75 (m, 2 H), 0.88-0.99 (m, 2 H), 1.41-1.58 (m, 3 H),1.58-1.65 (m, 1 H), 1.77-1.88 (m, 0.5 H), 1.91-1.99 (m, 0.5 H),2.09-2.20 (m, 2 H), 2.37 (dt, J = 14.3, 7.4 Hz, 0.5 H), 2.48 (dt, J =15.3, 7.5 Hz, 0.5 H), 3.02 (dd, J = 10.0, 7.7 Hz, 0.5 H), 3.30 (dt, J =12.3, 7.8 Hz, 0.5 H), 3.45- 3.57 (m, 1.5 H), 3.58-3.70 (m, 1.5 H),3.72-3.82 (m, 1.5 H), 3.98-4.09 (m, 4 H), 7.43-7.48 (m, 1 H), 7.70-7.77(m, 2 H), 7.85 (dd, J = 8.3, 1.5 Hz, 1 H), 7.88- 7.99 (m, 3 H), 8.22(dd, J = 8.3 Hz, 1 H), 8.38 (s, 1 H), 8.95-9.01 (m, 1 H) MS m/z 509.2(M + H)+ 662

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one ¹HNMR (400 MHz, CHLOROFORM-d) δ ppm 1.17 (dd, J = 12.8, 6.5 Hz, 3 H),1.34- 1.52 (m, 3 H), 1.52-1.70 (m, 2 H), 1.70- 1.95 (m, 1 H), 2.01-2.14(m, 2 H), 2.25- 2.52 (m, 1 H), 2.94-3.08 (m, 1 H), 3.19- 3.36 (m, 2 H),3.40-3.69 (m, 3 H), 3.88- 4.03 (m, 3 H), 4.03-4.19 (m, 1 H), 7.39 (dd, J= 8.2, 4.1 Hz, 1 H), 7.62-7.69 (m, 2 H), 7.74-7.80 (m, 1 H), 7.82-7.87(m, 2 H), 7.89 (m, J = 8.5 Hz, 1 H), 8.16 (d, J = 7.8 Hz, 1 H), 8.30(br. s., 1 H), 8.91 (dd, J = 4.1, 1.6 Hz, 1 H) MS m/z 513.2 (M + H)+ 663

2-(4-Quinolin-7-ylphenyl)-3-({(3R)-1- [(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm1.43-1.63 (m, 4 H), 1.79-2.04 (m, 4 H), 2.05-2.20 (m, 3 H), 2.39 (dq, J= 18.4, 7.3 Hz, 1 H), 3.04 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.10 (dd, J =10.8, 7.4 Hz, 0.5 H), 3.30-3.40 (m, 1 H), 3.45-3.57 (m, 1 H), 3.60-3.71(m, 1.5 H), 3.71- 3.77 (m, 1.5 H), 3.77-3.84 (m, 1 H), 3.85- 3.95 (m, 1H), 3.98-4.09 (m, 4 H), 4.35 (t, J = 6.6 Hz, 0.5 H), 4.37-4.43 (m, 0.5H), 7.43-7.48 (m, 1 H), 7.68-7.78 (m, 2 H), 7.83-7.88 (m, 1 H),7.89-7.99 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38 (s, 1 H), 8.95-9.01(m, 1 H) MS m/z 539.2 (M + H)+ 664

Methyl (3S)-3-{[4-oxo-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-3-yl]methyl}pyrrolidine-1-carboxylate MS m/z 499.3 (M + H)+ 665

3-{[(3S)-1-(Pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one ¹H NMR(600 MHz, CHLOROFORM-d) δ ppm 1.38-1.50 (m, 1 H), 1.50-1.58 (m, 2 H),1.70-1.85 (m, 5 H), 2.09-2.19 (m, 2 H), 2.28-2.42 (m, 1 H), 3.00 (dd, J= 10.6, 7.2 Hz, 1 H), 3.18-3.30 (m, 6 H), 3.33 (dd, J = 10.4, 7.0 Hz, 1H), 3.69 (m, J = 14.4, 7.2 Hz, 1 H), 3.75 (dd, J = 14.7, 7.9 Hz, 1 H),3.97-4.10 (m, 4 H), 7.46 (dd, J = 8.3, 4.2 Hz, 1 H), 7.73 (d, 2 H), 7.85(dd, J = 8.7, 1.9 Hz, 1 H), 7.89-7.93 (m, 2 H), 7.95 (d, J = 8.3 Hz, 1H), 8.22 (d, J = 7.6 Hz, 1 H), 8.36-8.40 (m, 1 H), 8.98 (dd, J = 4.2,1.5 Hz, 1 H) MS m/z 538.2 (M + H)+ 666

2-(4-Quinolin-7-ylphenyl)-3-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 552.1 (M +H)+ 667

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (600 MHz,CHLOROFORM-d) δ ppm −0.06-0.02 (m, 3 H), 0.68-0.73 (m, 2 H), 0.86-1.00(m, 2 H), 1.41-1.57 (m, 3 H), 1.78-1.86 (m, 0.5 H), 1.88-2.00 (m, 0.5H), 2.07-2.20 (m, 2 H), 2.35 (m, 0.5 H), 2.47 (dt, J = 15.2, 7.3 Hz, 0.5H), 3.01 (dd, J = 11.9, 7.0 Hz, 0.5 H), 3.21 (dd, J = 10.0, 7.7 Hz, 0.5H), 3.29 (dt, J = 12.3, 7.8 Hz, 0.5 H), 3.44-3.56 (m, 1.5 H), 3.56-3.69(m, 1.5 H), 3.71-3.79 (m, 1.5 H), 3.98-4.10 (m, 4 H), 6.85 (d, J = 1.5Hz, 1 H), 7.55 (dd, J = 8.3, 1.9 Hz, 1 H), 7.61 (dd, J = 8.7, 2.3 Hz, 1H), 7.64-7.71 (m, 3 H), 7.74-7.80 (m, 2 H), 7.84 (d, J = 1.9 Hz, 1 H) MSm/z 498.2 (M + H)+ 668

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(2-hydroxypropanoyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.13-1.35 (m, 3 H), 1.42-1.72 (m, 3 H), 1.76-2.04(m, 1 H), 2.04-2.22 (m, 2 H), 2.29-2.43 (m, 1 H), 2.43-2.65 (m, 1 H),3.09 (d, J = 16.1 Hz, 1 H), 3.23-3.44 (m, 2 H), 3.52-3.64 (m, 1 H),3.64-3.80 (m, 2 H), 3.96-4.11 (m, 3 H), 4.11-4.29 (m, 1 H), 6.86 (s, 1H), 7.49-7.74 (m, 5 H), 7.75-7.91 (m, 3 H) MS m/z 502.3 (M + H)+ 669

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm1.39-1.60 (m, 4 H), 1.76-1.93 (m, 2 H), 1.93-2.05 (m, 2 H), 2.05-2.18(m, 3 H), 2.38 (dq, J = 15.5, 7.7 Hz, 1 H), 3.02 (dd, J = 12.3, 7.4 Hz,0.5 H), 3.08 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.31-3.41 (m, 1 H),3.42-3.57 (m, 1 H), 3.58-3.76 (m, 3 H), 3.76-3.85 (m, 1 H), 3.85-3.95(m, 1 H), 3.98-4.11 (m, 4 H), 4.34 (dd, J = 7.2, 5.7 Hz, 0.5 H), 4.40(dd, J = 7.6, 6.0 Hz, 0.5 H), 6.85 (s, 1 H), 7.56 (d, J = 8.7 Hz, 1 H),7.61 (dd, J = 8.5, 3.6 Hz, 1 H), 7.63- 7.72 (m, 2 H), 7.74-7.80 (m, 2H), 7.84 (s, 1 H) MS m/z 528.2 (M + H)+ 670

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(trifluoroacetyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 526.1 (M + H)+ 671

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 527.2 (M +H)+ 672

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 512.2 (M +H)+ 673

3-{[(3R)-1-(2- Hycdroxypropanoyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 516.3 (M + H)+ 674

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 542.2 (M + H)+ 675

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- {[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 541.2 (M + H)+ 676

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm0.68-0.74 (m, 2 H), 0.86-0.99 (m, 2 H), 1.38-1.54 (m, 2 H), 1.79-1.88(m, 0.5 H), 1.89-2.00 (m, 0.5 H), 2.21-2.29 (m, 1 H), 2.3-2.53 (m, 2 H),3.03 (ddd, J = 11.9, 7.0, 4.9 Hz, 0.5 H), 3.19-3.26 (m, 0.5 H), 3.30(dt, J = 12.1, 7.9 Hz, 0.5 H), 3.46-3.57 (m, 1.5 H), 3.57-3.66 (m, 1 H),3.66-3.72 (m, 0.5 H), 3.72-3.82 (m, 1.5 H), 3.97 (s, 3 H), 3.99-4.07 (m,2 H), 4.16-4.29 (m, 2 H), 7.54-7.61 (m, 2 H), 7.64 (d, J = 8.3 Hz, 2 H),7.66-7.70 (m, 3 H), 77.3-7.79 (m, 2 H), 7.82 (s, 1 H) MS m/z 524.3 (M +H)+ 677

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.19-1.32 (m, 3 H), 1.41-1.71 (m, 1 H), 1.91-2.01(m, 1 H), 2.19-2.57 (m, 3 H), 3.01-3.18 (m, 1 H), 3.26-3.43 (m, 2 H),3.60 (dd, J = 12.2, 6.9 Hz, 1 H), 3.67- 3.79 (m, 2 H), 3.98 (s, 3 H),4.00-4.07 (m, 2 H), 4.09-4.31 (m, 3 H), 7.55-7.62 (m, 2 H), 7.62-7.71(m, 5 H), 7.73-7.80 (m, 2 H), 7.83 (s, 1 H) MS m/z 528.3 (M + H)+ 678

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 554.3 (M + H)+ 679

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 553.2 (M + H)+ 680

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δppm 0.65-0.76 (m, 2 H), 0.88-1.01 (m, 2 H), 1.41-1.56 (m, 1.5 H),1.59-1.65 (m, 0.5 H), 1.81-1.90 (m, 0.5 H), 1.91- 2.02 (m, 0.5 H),2.22-2.32 (m, 1 H), 2.31- 2.55 (m, 2 H), 3.04 (ddd, J = 11.9, 7.0, 4.9Hz, 0.5 H), 3.21-3.28 (m, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H),3.48- 3.58 (m, 1.5 H), 3.58-3.85 (m, 3 H), 3.99- 4.07 (m, 2 H),4.15-4.29 (m, 2 H), 7.42- 7.48 (m, 1 H), 7.71-7.78 (m, 2 H), 7.85 (dd, J= 8.5, 1.7 Hz, 1 H), 7.88-7.97 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38(s, 1 H) MS m/z 495.2 (M + H)+ 681

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one ¹HNMR (600 MHz, CHLOROFORM-d) δ ppm 1.20-1.31 (m, 3 H), 1.44-1.71 (m, 2H), 1.83-1.93 (m, 1 H), 1.97 (dt, J = 13.4, 6.5 Hz, 1 H), 2.21-2.31 (m,1 H), 2.33-2.59 (m, 2 H), 3.03-3.17 (m, 1 H), 3.27-3.43 (m, 2 H),3.57-3.66 (m, 1 H), 3.68-3.80 (m, 2 H), 3.99-4.08 (m, 2 H), 4.10-4.29(m, 3 H), 7.46 (dd, J = 8.1, 4.3 Hz, 1 H), 7.75 (dd, J = 8.5, 2.8 Hz, 2H), 7.81-7.89 (m, 1 H), 7.90-7.94 (m, 2 H), 7.96 (d, J = 8.7 Hz, 1 H),8.23 (d, J =8.3 Hz, 1 H), 8.36-8.41 (m, 1 H), 8.98 (dd, J = 4.2, 1.9 Hz,1 H) MS m/z 499.2 (M + H)+ 682

2-(4-Quinolin-7-ylphenyl)-3-({(3R)-1- [(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm1.38-2.22 (m, 6 H), 2.22-2.31 (m, 1 H), 2.31-2.50 (m, 2 H), 3.00-3.09(m, 0.5 H), 3.13 (ddd, J = 10.4, 7.6, 2.5 Hz, 0.5 H), 3.30-3.43 (m, 1H), 3.46-3.59 (m, 1 H), 3.58-3.85 (m, 4 H), 3.85-3.96 (m, 1 H),3.97-4.09 (m, 2 H), 4.16-4.29 (m, 2 H), 4.36 (t, J = 6.0 Hz, 0.5 H),4.38-4.44 (m, 0.5 H), 7.44-7.51 (m, 1 H), 7.70- 7.79 (m, 2 H), 7.84-7.89(m, 1 H), 7.89- 7.95 (m, 2 H), 7.96 (dd, J = 8.5, 2.8 Hz, 1 H), 8.25 (d,J = 7.9 Hz, 1 H), 8.41 (s, 1 H), 8.93-9.01 (m, 1 H) MS m/z 525.3 (M +H)+ 683

Methyl (3S)-{[4-oxo-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-3-yl]methyl}pyrrolidin-1-carboxylate MS m/z 458.2 (M + H)+ 684

2-(4-Quinolin-7-ylphenyl)-3-{[(3R)-1-(trifluoroacetyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 523.1 (M + H)+ 685

3-{[(3S)-1-(Pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z524.2 (M + H)+ 686

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one ¹H NMR (600 MHz,CHLOROFORM-d) δ ppm 0.64-0.77 (m, 2 H), 0.85-1.01 (m, 2 H), 1.40-1.55(m, 1.5 H), 1.84 (td, J = 11.7, 6.8 Hz, 0.5 H), 1.89-2.02 (m, 0.5 H),2.21-2.30 (m, 1 H), 2.30-2.57 (m, 2 H), 3.03 (ddd, J = 10.1, 7.6, 6.0Hz, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.47- 3.57 (m, 1.5 H),3.57-3.66 (m, 1 H), 3.66- 3.73 (m, 0.5 H), 3.73-3.85 (m, 1.5 H),3.97-4.08 (m, 2 H), 4.14-4.30 (m, 2 H), 6.85 (d, J = 1.5 Hz, 1 H),7.53-7.58 (m, 1 H), 7.58-7.63 (m, 1 H), 7.64-7.72 (m, 3 H), 7.73-7.80(m, 2 H), 7.84 (d, J = 1.9 Hz, 1 H) MS m/z 484.2 (M + H)+ 687

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(2-hydroxypropanoyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.18-1.36 (m, 3 H), 1.38-1.59 (m, 1 H), 1.59-1.76(m, 1 H), 1.81-2.07 (m, 1 H), 2.22-2.49 (m, 2 H), 2.97-3.26 (m, 3 H),3.29-3.46 (m, 2 H), 3.62 (dd, J = 12.3, 6.5 Hz, 1 H), 3.69-3.81 (m, 2H),4.10-4.10 (m, 2 H), 4.18-4.30 (m, 2 H), 6.86 (d, J = 1.5 Hz, 1 H),7.52-7.59 (m, 1 H), 7.62 (m, J = 8.5 Hz, 1 H), 7.66-7.73 (m, 3 H),7.76-7.83 (m, 2 H), 7.83-7.88 (m, 1 H) MS m/z 488.1 (M + H)+ 688

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm1.38-1.61 (m, 2 H), 1.78-2.07 (m, 4 H), 2.06-2.21 (m, 1 H), 2.21-2.30(m, 1 H), 2.30-2.49 (m, 2 H), 3.05 (ddd, J = 12.2, 7.5, 3.0 Hz, 0.5 H),3.08-3.15 (m, 0.5 H), 3.29-3.42 (m, 1 H), 3.46- 3.58 (m, 1 H), 3.58-3.78(m, 3 H), 3.78- 3.85 (m, 1 H), 3.85-3.95 (m, 1 H), 3.96- 4.07 (m, 2 H),4.13-4.28 (m, 2 H), 4.31- 4.38 (m, 0.5 H), 4.38-4.44 (m, 0.5 H), 6.85(s, 1 H), 7.53-7.58 (m, 1 H), 7.58- 7.64 (m, 1 H), 7.64-7.73 (m, 3 H),7.77 (dd, J = 8.3, 5.3 Hz, 2 H), 7.85 (s, 1 H) MS m/z 514.2 (M + H)+ 689

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 513.2 (M +H)+ 690

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 498.2 (M +H)+ 691

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 502.3 (M + H)+ 692

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}metrhyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 528.2 (M + H)+ 693

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- {[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 527.2 (M + H)+ 694

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 524.3 (M + H)+ 695

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 524.3 (M + H)+ 696

2-[4′-(1-Mehtyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 554.2 (M + H)+ 697

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[1-(pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 553.3 (M + H)+ 698

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δppm 0.63-0.73 (m, 2 H), 0.84-0.94 (m, 2 H), 1.24-1.32 (m, 1 H),1.48-1.55 (m, 2 H), 2.07-2.18 (m, 2 H), 2.72-2.82 (m, 1 H), 3.58 (dd, J= 9.8, 5.7 Hz, 1 H), 3.87- 4.07 (m, 8 H), 4.20 (t, J = 8.3 Hz, 1 H),7.46 (dd, J = 8.3, 4.2 Hz, 1 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.85 (dd, J= 8.3, 1.9 Hz, 1 H), 7.93 (d, J = 8.7 Hz, 2 H), 7.96 (d, J = 8.3 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1 H), 8.36- 8.40 (m, 1 H), 8.98 (dd, J = 4.2,1.9 Hz, 1 H) MS m/z 495.2 (M + H)+ 699

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 499.2 (M + H)+ 700

2-(4-Quinolin-7-ylphenyl)-3-({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one ¹H NMR (600 MHz,CHLOROFORM-d) δ ppm 1.51 (d, J = 13.2 Hz, 2 H), 1.77-1.91 (m, 2 H),1.98-2.18 (m, 4 H), 2.71-2.80 (m, 1 H), 3.57-3.64 (m, 1 H), 3.72-3.85(m, 2 H), 3.86-4.06 (m, 8 H), 4.18-4.37 (m, 2 H), 7.46 (dd, J = 8.3, 4.2Hz, 1 H), 7.72 (dd, J = 8.3, 4.5 Hz, 2 H), 7.85 (d, J = 8.3 Hz, 1 H),7.92 (d, 2 H), 7.96 (d, J = 8.3 Hz, 1 H), 8.22 (d, J = 8.3 Hz, 1 H),8.38 (s, 1 H), 8.98 (dd, J = 4.2, 1.5 Hz, 1 H) MS m/z 525.2 (M + H)+ 701

3-{[1-(Pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 524.2 (M + H)+ 702

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 484.2 (M +H)+ 703

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(2-hydroxypropanoyl)azetidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 488.2 (M + H)+ 704

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({1- [(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 514.2 (M + H)+ 705

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 513.2 (M +H)+ 706

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.9, 3.1 Hz, 2 H), 0.85- 0.94 (m, 2H), 1.22-1.33 (m, 1 H), 1.51 (d, J = 13.6 Hz, 2 H), 2.12 (ddd, J = 13.7,9.0, 5.4 Hz, 2 H), 2.70-2.83 (m, 1 H), 3.57 (dd, J = 9.7, 5.6 Hz, 1 H),3.85-3.93 (m,m 2 H), 3.93-4.00 (m, 2 H), 4.00-4.07 (m, 4 H), 4.14 (s, 3H), 4.20 (t, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1 H), 7.63-7.71 (m, 3H), 7.80 (d, J = 8.3 Hz, 2 H), 7.95- 8.00 (m, 1 H), 8.07 (d, J = 1.0 Hz,1 H) MS m/z 498.2 (M + H)+ 707

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 502.2 (M +H)+ 708

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 528.2 (M + H)+ 709

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3-{[1-(pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 1.46-1.55 (m, 2 H), 1.76 (dt, J = 6.5, 3.5 Hz, 4 H),2.12 (ddd, J = 13.7, 8.8, 5.5 Hz, 2 H), 2.59-2.72 (m, 1 H), 3.17-3.25(m, 4 H), 3.54 (dd, J = 8.2, 5.6 Hz, 2 H), 3.85-3.94 (m, 4 H), 4.00-4.07(m, 4 H), 4.14 (s, 3 H), 7.51 (d, J = 8.8 Hz, 1 H), 7.63-7.71 (m, 3 H),7.79 (d, J = 8.3 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s, 1 H) MS m/z 527.3(M + H)+ 710

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 510.3 (M + H)+ 711

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 514.2 (M + H)+ 712

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-3-({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 540.2 (M + H)+ 713

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[1-(pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 539.2 (M + H)+ 714

3-{[1-(Cycloprppylcarbonyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 481.2 (M + H)+ 715

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δppm 1.16-1.30 (m, 3 H), 2.26 (dt, J = 12.4, 6.0 Hz, 1 H), 2.37-2.50 (m,1 H), 2.78-2.96 (m, 1 H), 3.61-3.70 (m, 0.5 H), 3.73 (dd, J = 10.5, 5.5Hz, 0.5 H), 3.78- 3.86 (m, 0.5 H), 3.86-4.06 (m, 6 H), 4.06-4.18 (m, 2.5H), 4.18-4.29 (m, 2.5 H), 7.48 (dd, J = 8.3, 4.3 Hz, 1 H), 7.69- 7.78(m, 2 H), 7.82-7.90 (m, 1 H), 7.90- 8.01 (m, 3 H), 8.24 (d, J = 8.3 Hz,1 H), 8.40 (br. s., 1 H), 8.99 (dd, J = 4.3, 1.5 Hz, 1 H) MS m/z 485.2(M + H)+ 716

2-(4-Quinolin-7-ylphenyl)-3-({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 511.3 (M +H)+ 717

3-{[1-(Pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-2-(4-quinolin-7-ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 510.2 (M + H)+ 718

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 470.2 (M +H)+ 719

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(2-hydroxypropanoyl)azetidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 474.1 (M + H)+ 720

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({1- [(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 500.2 (M + H)+ 721

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(pyrrolidin-1-ylcarbonyl)azetidin-3-yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 499.3 (M +H)+ 722

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 484.3 (M +H)+ 723

3-{[1-(2-Hydroxypropanoyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 488.2 (M +H)+ 724

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({1-[(2R)-tetrahydro-furan-2-ylcarbonyl]azetidin-3-yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 514.2 (M + H)+ 725

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-6-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δppm 0.65-0.76 (m, 2 H), 0.85-1.00 (m, 2 H), 1.39-1.55 (m, 1.5 H),1.79-1.90 (m, 0.5 H), 1.96 (td, J = 12.3, 6.8 Hz, 0.5 H), 2.37 (br. s.,0.5 H), 2.44-2.55 (m, 0.5 H), 3.02 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.21-3.27 (m, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.46-3.58 (m, 1.5H), 3.58-3.82 (m, 6 H), 3.97 (s, 3 H), 4.28-4.33 (m, 2 H), 4.33-4.38 (m,2 H), 7.56-7.61 (m, 2 H), 7.62-7.66 (m, 2 H), 7.66-7.71 (m, 3 H),7.74-7.80 (m, 2 H), 7.82 (s, 1 H) MS m/z 567.3 (M + H)+ 726

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}-6-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-8-oxo-2,5,7-triazaspiro[3.4]oct-5- ene-2-carboxylate ¹H NMR (400MHz, CHLOROFORM-d) δ ppm 1.26 (t, J = 6.9 Hz, 3 H), 1.39-1.65 (m, 1 H),1.59-1.73 (m, 1.5 H), 1.83- 2.04 (m, 1.5 H), 2.32-2.47 (m, 0.5 H),2.48-2.60 (m, 0.5 H), 3.00-3.18 (m, 1 H), 3.28-=3.44 (m, 2 H), 3.54-3.66(m, 1 H), 3.68-3.79 (m, 5 H), 3.98 (s, 3 H), 4.08-4.24 (m, 1 H),4.29-4.40 (m, 4 H), 7.57-7.62 (m, 2 H), 7.62-7.72 (m, 5 H), 7.75-7.81(m, 2 H), 7.83 (s, 1 H) MS m/z 571.3 (M + H)+ 727

Methyl 6-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-8-oxo-7-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7-triazaspiro[3.4]ect-5-ene- 2-carboxylate ¹H NMR (600MHz, CHLOROFORM-d) δ ppm 1.38-1.61 (m, 1.5 H), 1.78-2.24 (m, 5.5 H),2.42 (m, 1 H), 3.04 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.13 (dd, J = 10.6,7.2 Hz, 0.5 H), 3.37 (dq, J = 11.3, 7.8 Hz, 1 H), 3.46-3.58 (m, 1 H),3.59-3.77 (m, 6 H), 3.78-3.84 (m, 1 H), 3.84-3.94 (m, 1 H), 3.98 (s, 3H), 4.27-4.38 (m, 4.5 H), 4.38-4.43 (m, 0.5 H), 7.56-7.62 (m, 2 H),7.62-7.72 (m, 5 H), 7.75-7.80 (m, 2 H), 7.80-7.84 (m, 1 H) MS m/z 597.4(M + H)+ 728

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxo-6-(4-quinolin-7-ylphenyl)-2,5,7-triazaspiro[3.4]ect-5-ene- 2-carboxylate ¹H NMR (600MHz, CHLOROFORM-d) δ ppm 0.60-0.77 (m, 2 H), 0.84-1.01 (m, 2 H),1.36-1.56 (m, 2 H), 1.79-1.92 (m, 0.5 H), 1.92-2.03 (m, 0.5 H),2.30-2.46 (m, 0.5 H), 2.51 (m, 0.5 H), 3.04 (dd, J = 12.1, 7.2 Hz, 0.5H), 3.22-3.29 (m, 1 H), 3.29-3.36 (m, 0.5 H), 3.48-3.59 (m, 1.5 H),3.59-3.85 (m, 6 H), 4.25-4.42 (m, 4 H), 7.41-7.50 (m, 1 H), 7.76 (t, J =8.3 Hz, 2 H), 7.85 (dd, J = 8.7, 1.9 Hz, 1 H), 7.88-8.00 (m, 3 H), 8.21(d, J = 7.9 Hz, 1 H), 8.37 (s, 1 H), 8.90-9.01 (m, 1 H) MS m/z 538.2(M + H)+ 729

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}-8-oxo-6-(4-quinolin-7-ylphenyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δppm 1.17-1.31 (m, 3 H), 1.45-1.57 (m, 1 H), 1.90 (m, 0.5 H), 1.98 (m,0.5 H), 2.31-2.48 (m, 0.5 H), 2.49-2.61 (m, 0.5 H), 3.07 (dd, J = 12.3,6.2 Hz, 0.5 H), 3.11- 3.19 (m, 0.5 H), 3.27-3.44 (m, 2 H), 3.57-3.65 (m,1 H), 3.67-3.79 (m, 2 H), 3.74 (s, 3 H), 4.14 (q, J = 6.3 Hz, 0.5 H),4.20 (q, J = 6.5 Hz, 0.5 H), 4.28-4.41 (m, 4 H), 7.46 (dd, J = 12.5, 4.3Hz, 1 H), 7.75 (dd, J = 8.3, 3.4 Hz, 2 H), 7.80-7.89 (m, 1 H), 7.87-7.99(m, 3 H), 8.23 (d, J = 8.3 Hz, 1 H), 8.39 (d, J = 4.9 Hz, 1 H), 8.92-9.04 (m, 1 H) MS m/z 542.3 (M + H)+ 730

Methyl 8-oxo-6-(4-quinolin-7-ylphenyl)-7-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δppm 1.41-1.56 (m, 1 H), 1.78-1.90 (m, 1.5 H), 1.90-2.07 (m, 2.5 H),2.07-2.15 (m, 0.5 H), 2.15-2.23 (m, 0.5 H), 2.44 (m, 1 H), 3.06 (dd, J =12.1, 7.2 Hz, 0.5 H), 3.15 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.29- 3.44 (m,1 H), 3.47-3.59 (m, 1 H), 3.60- 3.86 (m, 4 H), 3.73 (s, 3 H), 3.85-3.95(m, 1 H), 4.28-4.39 (m, 4 H), 4.38-4.44 (m, 1 H), 7.42-7.51 (m, 1 H),7.76 (dd, J = 12.5, 8.3 Hz, 2 H), 7.86 (d, J = 8.3 Hz, 1 H), 7.89-8.01(m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.36 (s, 1 H), 8.93-9.04 (m, 1 H)MS m/z 568.3 (M + H)+ 731

Methyl 8-oxo-6-(4-quinolin-7-ylphenyl)-7-{[(3R)-1-(trifluoroacetyl)pyrrolidin-3-yl]methyl}-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 566.1(M + H)+ 732

Methyl 8-oxo-7-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-6-(4- quinolin-7-ylphenyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 567.2 (M + H)+ 733

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-7-{[(3R)-1-(cycloprropylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate ¹H NMR(600 MHz, CHLOROFORM-d) δ ppm 0.72 (m, 2 H), 0.86-1.01 (m, 2 H),1.39-1.55 (m, 1.5 H), 1.64 (m, 1 H), 1.81- 1.91 (m, 0.5 H), 1.92-2.04(m, 0.5 H), 2.38 (br. s., 0.5 H), 2.44-2.56 (m, 0.5 H), 3.02 (dd, J =11.9, 7.0 Hz, 0.5 H), 3.25 (dd, J = 10.0, 7.7 Hz, 0.5 H), 3.32 (dt, J =12.1, 7.9 Hz, 0.5 H), 3.48-3.57 (m, 1.5 H), 3.58-3.72 (m, 1.5 H), 3.75(s, 3 H), 3.74- 3.81 (m, 1 H), 4.26-4.39 (m, 4 H), 6.85 (d, J = 2.3 Hz,1 H), 7.56 (dd, J = 8.3, 1.9 Hz, 1 H), 7.57-7.64 (m, 1 H), 7.65-7.73 (m,3 H), 7.74-7.82 (m, 2 H), 7.85 (d, J = 1.5 Hz, 1 H) MS m/z 527.3 (M +H)+ 734

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-7-{[(3R)-1-(2-hydroxypropanoyl)pyrrolidin-3-yl]methyl}-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z531.2 (M + H)+ 735

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-8-oxo-7-({(3R)-1-[(2T)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δppm 1.42-1.55 (m, 0.5 H), 1.78-2.07 (m, 4 H), 2.06-2.23 (m, 1 H),2.31-2.50 (m, 1 H), 3.04 (dd, J = 12.5, 7.2 Hz, 0.5 H), 3.13 (dd, J =10.6, 7.2 Hz, 0.5 H), 3.30- 3.41 (m, 1 H), 3.47-3.58 (m, 1 H), 3.60-3.69 (m, 1 H), 3.68-3.77 (m, 4.5 H), 3.81 (q, J = 6.7 Hz, 1 H),3.84-3.94 (m, 1 H), 4.27-4.38 (m, 4 H), 4.38-4.43 (m, 0.5 H), 6.82-6.87(m, 1 H), 7.54-7.59 (m, 1 H), 7.61 (dd, J = 8.7, 3.8 Hz, 1 H), 7.63-7.73 (m, 3 H), 7.78 (dd, J = 8.3, 6.0 Hz, 2 H), 7.85 (s, 1 H) MS m/z557.2 (M + H)+ 736

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-8- oxo-7-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-2,5,7-triazaspiro[3.4]oct-5-ene-3-carboxylate MS m/z 556.2 (M + H)+ 737

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-6-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate ¹H NMR(600 MHz, CHLOROFORM-d) δ ppm 0.63-0.77 (m, 2 H), 0.87-1.01 (m, 2 H),1.41-1.55 (m, 1.5 H), 1.80-1.91 (m, 0.5 H), 1.92-2.02 (m, 0.5 H), 2.38(br. s., 0.5 H), 2.43-2.57 (m, 0.5 H), 3.02 (dd, J = 12.1, 7.2 Hz, 0.5H), 3.49-3.57 (m, 1.5 H), 3.60-3.80 (m, 6 H), 4.13 (s, 3 H), 4.29-4.34(m, 2 H), 4.34-4.38 (m, 2 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.66-7.73 (m, 3H), 7.77-7.83 (m, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H) MS m/z 541.3 (M +H)+ 738

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}-6-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 545.2 (M + H)+739

Methyl 6-[4-(1-methyl-1H-indazol-5-yl yl)phenyl]-8-oxo-7-({(3R)-1-[(2R)-tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate ¹H NMR (600MHz, CHLOROFORM-d) δ ppm 1.44-1.54 (m, 1 H), 1.79-2.22 (m, 5.5 H),2.32-2.52 (m, 1 H), 3.04 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.14 (dd, J =10.6, 7.2 Hz, 0.5 H), 3.31-3.41 (m, 1 H), 3.48- 3.58 (m, 1 H), 3.59-3.78(m, 6.5 H), 3.78- 3.84 (m, 1 H), 3.84-3.95 (m, 1 H), 4.10- 4.15 (m, 3H), 4.29-4.38 (m, 4.5 H), 4.38-4.44 (m, 0.5 H), 7.51 (dd, J = 8.7, 3.4Hz, 1 H), 7.66-7.73 (m, 3 H), 7.77- 7.83 (m, 2 H), 7.98 (s, 1 H),8.05-8.08 (m, 1 H) MS m/z 571.2 (M + H)+ 740

Methyl 6-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-oxo-7-{[(3S)-1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3-yl]methyl}-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 570.2 (M + H)+ 741

8-Acryloyl-2-[4-(1-benzofuran-6- yl)phen yl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en- 4-one ¹H NMR (400 MHz, CDCl3)d 0.71-0.72 (m, 2 H), 0.88-0.98 (m, 3 H), 1.44-1.65 (m, 5 H), 2.30-2.48(m, 2 H), 3.01-3.31 (m, 2 H), 3.50-3.79 (m, 6 H), 4.00-4.07 (m, 1 H),4.50-4.59 (m, 1 H), 5.72 (d, J = 10.6 Hz, 1 H), 6.34 (m, 1 H), 6.63 (dd,J = 10.6, 16.7 Hz, 1 H), 6.85 (d, J = 1.5 Hz, 1 H), 7.54-7.70 (m, 5 H),7.76-7.80 (m, 2 H), 7.84 (s, 1 H) MS m/z 551.2 (M + H)+ 742

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz,CDCl3) d 0.61- 0.87 (m, 5 H), 1.40-1.57 (m, 4 H), 1.75- 2.10 (m, 4 H),2.30 (s, 3 H), 2.45 (s, 3 H), 2.61 (t, J = 5.0 Hz, 1 H), 2.68-2.75 (m, 1H), 2.85-2.97 (m, 3 H), 3.10-3.25 (m, 1 H), 3.39-3.70 (m, 8 H), 7.45(dd, J = 1.4, 8.2 Hz, 1 H), 7.59 (dd, J = 2.7, 8.2 Hz, 2 H), 7.72-7.77(m, 4 H) MS m/z 585 (M + H)+ 743

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (400 MHz,CDCl3) d 0.61- 0.87 (m, 5 H), 1.40-1.57 (m, 4 H), 1.75- 2.10 (m, 4 H),2.30 (s, 3 H), 2.45 (s, 3 H), 2.61 (t, J = 5.0 Hz, 1 H), 2.68-2.75 (m, 1H), 2.85-2.97 (m, 3 H), 3.10-3.25 (m, 1 H), 3.39-3.70 (m, 8 H), 7.45(dd, J = 1.4, 8.2 Hz, 1 H), 7.59 (dd, J = 2.7, 8.2 Hz, 2 H), 7.72-7.77(m, 4 H) MS m/z 539 (M + H)+ 744

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (400 MHz,CDCl3) d 0.6-1.0 (m, 5 H), 1.05-1.20 (m, 6 H), 1.25-3.60 (m, 18 H), 6.58(s, 1 HG), 7.47 (s, 1 H), 7.51-7.60 (m, 2 H), 7.78-7.82 (m, 2 H), 7.91(d, J = 7.0 Hz, 2 H), 7.99 (s, 1 H), 11.28 (s, 1 H) MS m/z 538 (M + H)+745

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.55-0.65 (m, 4 H), 1.35-2.40 (m, 7 H), 2.85-3.71 (m, 10H), 2.96 (s, 3 H), 6.53 (s, 1 H), 7.41 (t, J = 2.6 Hz, 1 H), 7.48-7.54(m, 2 H), 7.75-7.79 (m, 2 H), 7.86-7.88 (m, 2 H), 7.94 (s, 1 H), 11.21(s, 1 H) MS m/z 574 (M + H)+ 746

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.65 (m, 4 H), 1.20-2.35 (m, 7 H),2.79-3.65 (m, 10 H), 2.92 (s, 3 H), 7.01 (d, J = 1.9 Hz, 1 H), 7.64-7.71(m, 2 H), 7.75-7.78 (m, 2 H), 7.84-7.88 (m, 2 H), 8.00-8.03 (m, 2 H) MSm/z 575 (M + H)+ 747

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62-0.67(m, 4 H), 1.32-1.95 (m, 7 H), 2.15-2.38 (m, 1 H), 2.52-2.60 (m, 3 H),2.83-2.89 (m, 3 H), 3.07-3.15 (m, 2 H), 3.32 (s, 3 H), 3.45-3.70 (m, 6H), 6.53 (s, 1 H), 7.41 (t, J = 2.6 Hz, 1 H), 7.46-7.54 (m, 2 H),7.73-7.77 (m, 2 H), 7.84-7.87 (m, 2 H), 7.94 (s, 1 H), 11.22 (s, 1 H) MSm/z 554 (M + H)+ 748

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indazxol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8-trisazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm0.60-0.67 (m, 4 H), 1.35-1.95 (m, 7 H), 2.15-2.35 (m, 1 H), 2.50-2.60(m, 3 H), 2.80-2.90 (m, 3 H), 3.05-3.15 (m, 2 H), 3.26 (s, 3 H),3.45-3.69 (m, 6 H), 7.66- 7.69 (m, 1 H), 7.75-7.80 (m, 3 H), 7.88- 7.91(m, 2 H), 8.16 (d, J = 5.2 Hz, 2 H), 13.18 (s, 1 H) MS m/z 555 (M + H)+749

2-[4-(1-Benzofurann-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.65-0.70 (m, 4 H), 1.42-2.0 (m, 7 H),2.20-2.45 (m, 1 H), 2.55-2.65 (m, 3 H), 2.85-2.92 (m, 3 H), 3.10-3.35(m, 2 H), 3.31 (s, 3 H), 3.48-3.65 (m, 4 H), 3.69- 3.74 (m, 2 H), 7.10(d, J = 1.7 Hz, 1 H), 7.75-7.86 (m, 4 H), 7.92-7.95 (m, 2 H), 8.09-8.13(m, 2 H) MS m/z 555 (M + H)+ 750

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-methoxyethyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.70 (m, 4 H), 1.26-1.99 (m, 7 H),2.11-2.38 (m, 1 H), 2.56 (t, J = 5.9 Hz, 3 H), 2.75-2.91 (m, 2.5 H),3.02-3.17 (m, 1 H), 3.17-3.24 (m, 0.5 H), 3.25 (s, 3 H), 3.35-3.59 (m, 4H), 3.65 (t, J = 7.2 Hz, 2 H), 4.09 (s, 3 H), 7.72-7.85 (m, 4 H),7.85-7.94 (m, 2 H), 8.13 (s, 2 H) MS m/z 569 (M + H)+ 751

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.52-0.71 (m, 4 H), 1.26-1.97 (m, 7 H), 2.12-2.42 (m, 1H), 2.87 (dd, J = 11.3, 6.6 Hz, 0.5 H), 3.03-3.18 (m, 1 H), 3.19- 3.29(m, 1 H), 3.38-3.56 (m, 2.5 H), 3.63- 3.81 (m, 3 H), 3.95 (d, J = 13.9Hz, 1 H), 4.29 (d, J = 13.2, Hz, 1 H), 6.52 (br. s., 1 H), 7.40 (t, J =2.5 Hz, 1 H), 7.44-7.56 (m, 2 H), 77.2-7.83 (m, 2 H), 7.83-7.91 (m, 2H), 7.94 (s, 1 H), 11.21 (br. s., 1 H) MS m/z 592 (M + H)+ 752

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-(trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J = 5.4 Hz, 4 H), 1.29-1.98 (m, 7H), 2.12-2.40 (m, 1 H), 2.86 (dd, J = 11.5, 6.7 Hz, 0.5 H), 3.01-3.18(m, 1 H), 3.19- 3.29 (m, 1 H), 3.38-3.52 (m, 2.5 H), 3.63- 3.80 (m, 3H), 3.95 (d, J = 13.9 Hz, 1 H), 4.09 (s, 3 H), 4.29 (d, J = 13.7 Hz, 1H), 7.73-7.87 (m, 4 H), 7.92 (dd, J = 8.2, 2.1 Hz, 2 H), 8.14 (d, J =4.1 Hz, 2 H) MS m/z 607 (M + H)+ 753

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (2-methylpropanoyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.62-0.76 (m, 2 H), 0.91 (br. s., 2 H), 1.18 (t, J = 7.8 Hz, 6 H),1.22-1.36 (m, 1 H), 1.49-1.67 (m, 2 H), 1.86-2.10 (m, 2 H), 2.76 (br.s., 1 H), 2.80-2.97 (m, 1 H), 3.37-3.52 (m, 1 H), 3.59 (dd, J = 9.6, 5.6Hz, 1 H), 3.73 (t, J = 11.3 Hz, 1 H), 3.80-4.07 (m, 5 H), 4.19 (t, J =8.1 Hz, 1 H), 4.51 (d, J = 13.2 Hz, 1 H), 6.56-6.70 (m, 1 H), 7.27-7.35(m, 1 H), 7.42-7.56 (m, 2 H), 7.63 (d, J = 8.2 Hz, 2 H), 7.81 (d, J =8.2 Hz, 2 H), 7.91 (s, 1 H), 8.55 (br. s., 1 H) MS m/z 552 (M + H)+ 754

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (2-methylpropanoyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.62-0.77 (m, 2 H), 0.86-0.99 (m, 2 H), 1.18 (t, J = 7.8 Hz, 6 H),1.23-1.31 (m, 1 H), 1.50-1.80 (m, 4 H), 1.88-2.09 (m, 2 H), 2.80 (br.s., 1 H), 2.82-2.95 (m, 1 H), 3.35-3.51 (m, 1 H), 3.57 (dd, J = 9.5, 5.6Hz, 1 H), 3.63-3.82 (m, 1 H), 3.82-4.07 (m, 4 H), 4.21 (t, J = 8.2 Hz, 1H), 4.51 (d, J = 13.3 Hz, 1 H), 7.52-7.62 (m, 1 H), 7.66 (d, J = 7.8 Hz,3 H), 7.79 (d, J = 8.0 Hz, 2 H), 8.00 (s, 1 H), 8.17 (br. s., 1 H) MSm/z 553 (M + H)+ 755

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- triazaspiro[4.5]dec-1-en-4-one¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.77 (m, 2 H), 0.79-0.98 (m, 2H), 1.22-1.35 (m, 1 H), 1.59 (d, J = 12.8 Hz, 2 H), 2.05-2.27 (m, 3 H),2.60-2.84 (m, 5 H), 2.96 (d, J = 11.3 Hz, 2 H), 3.39 (s, 3 H), 3.58 (t,J = 5.4 Hz, 2 H), 3.76- 4.03 (m, 4 H), 4.17 (t, J = 8.0 Hz, 1 H), 6.64(br. s., 1 H), 7.28-7.36 (m, 1 H), 7.41-7.55 (m, 2 H), 7.61 (d, J = 8.1Hz, 2 H), 7.79 (d, J = 8.1 Hz, 2 H), 7.90 (s, 1 H), 8.44 (br. s., 1 H)MS m/z 540 (M + H)+ 756

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[2-(1H-indazol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.61-0.75 (m, 2 H), 0.85-0.94 (m, 2 H), 1.25-1.33 (m, 1 H), 1.59 (d, J =13.2 Hz, 2 H), 2.07-2.25 (m, 2 H), 2.62-2.84 (m, 5 H), 2.91-3.03 (m, 2H), 3.39 (s, 3 H), 3.55-3.62 (m, 2 H), 3.78-4.05 (m, 4 H), 4.19 (t, J =8.2 Hz, 1 H), 7.58 (m, J = 8.8 Hz, 1 H), 7.61-7.68 (m, 3 H), 7.71-7.86(m, 2 H), 7.99 (s, 1 H), 8.16 (s, 1 H), 10.56 (br. s., 1 H) MS m/z 541(M + H)+ 757

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1H- indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.69(dd, J = 7.5, 3.0 Hz, 2 H), 0.84- 0.95 (m, 2 H), 1.60 (d, J = 12.8 Hz, 2H), 1.98-2.23 (m, 3 H), 2.68 (t, J = 5.1 Hz, 2 H), 2.72-2.86 (m, 3 H),2.94 (d, J = 11.5 Hz, 2 H), 3.54-3.62 (m, 1 H), 3.62-3.73 (m, 2 H),3.77-4.04 (m, 4 H), 4.18 (t, J = 8.1 Hz, 1 H), 6.65 (br. s., 1 H), 7.29(br. s., 1 H), 7.41-7.58 (m, 2 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.80 (d, J= 8.1 Hz, 2 H), 7.91 (s, 1 H), 8.34 (br. s., 1 H) MS m/z 526 (M + H)+758

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1H- indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.63-0.77 (m, 2 H), 0.87-0.96 (m, 2 H), 1.25-1.32 (m, 2 H), 1.61 (d, J13.2 Hz, 2 H), 2.04-2.16 (m, 2 H), 2.69 (t, J = 5.2 Hz, 2 H), 2.73-2.86(m, 3 H), 2.88- 3.00 (m, 2 H), 3.54-3.62 (m, 1 H), 3.67 (t, J = 5.2 Hz,2 H), 3.78-4.04 (m, 4 H), 4.20 (t, J = 8.1 Hz, 1 H), 7.59 (m, J = 8.7Hz, ,1 H), 7.63-7.71 (m, 3 H), 7.78 (d, J = 8.1 Hz, 2 H), 8.00 (s, 1 H),8.16 (s, 1 H) MS m/z 527 (M + H)+ 759

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.63-0.75 (m, 2 H), 0.85-0.95 (m, 2 H), 1.19-1.34(m, 1 H), 1.54 (d, J = 13.3 Hz, 2 H), 1.87-2.03 (m, 2 H), 2.60-2.83 (m,1 H), 3.09-3.29 (m, 4 H), 3.56 (dd, J = 9.7, 5.7 Hz, 1 H), 3.80-3.97 (m,4 H), 3.98 (s, 3 H), 4.18 (t, J = 8.4 Hz, 1 H), 7.56- 7.70 (m, 7 H),7.77 (d, J = 8.2 Hz, 2 H), 7.83 (s, 1 H) MS m/z 523 (M + H)+ 760

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 0.59-0.78 (m, 2 H), 0.90 (br. s., 2H), 1.72 (br. s., 1 H), 2.16 (t, J = 10.0 Hz, 2 H), 2.66-2.81 (m, 1 H),2.85 (s, 3 H), 3.31-3.43 (m, 2 H), 3.54-3.64 (m, 1 H), 3.67-4.07 (m, 7H), 4.20 (t, J = 7.6 Hz, 1 H), 6.86 (br. s., 1 H), 7.52-7.73 (m, 5 H),7.75-7.92 (m, 3 H) MS m/z 561 (M + H)+ 761

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 0.61-0.77 (m, 2 H), 0.90 (br. s., 2H), 1.14-1.36 (m, 2 H), 2.06-2.25 (m, 2 H), 2.67-2.80 (m, 1 H), 2.85 (s,3 H), 3.29-3.63 (m, 3 H), 3.80 (d, J = 11.7 Hz, 2 H), 3.86-4.05 (m, 4H), 4.13 (s, 3 H), 4.16-4.26 (m, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.66(t, J = 8.7 Hz, 3 H), 7.81 (d, J = 8.0 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s,1 H) MS m/z 575 (M + H)+ 762

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.47-0.73 (m, 4 H), 1.30-1.45 (m, 1 H), 1.62 (d, J = 12.8Hz, 2 H), 1.91 (t, J = 10.3 Hz, 2 H), 2.56-2.71 (m, 1 H), 2.95 (s, 3 H),3.21 (t, J = 10.3 Hz, 2 H), 3.61 (d, J = 11.5 Hz, 2 H), 3.67-3.82 (m, 2H), 3.88 (d, J = 7.3 Hz, 2 H), 4.15 (t, J = 8.3 Hz, 1 H), 6.52 (br. s.,1 H), 7.41 (br. s., 1 H), 7.44-7.58 (m, 2 H), 7.74 (d, J = 8.1 Hz, 2 H),7.87 (d, J = 8.0 Hz, 2 H), 7.94 (s, 1 H) MS m/z 560 (M + H)+ 763

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8-(methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.51-0.70 (m, 4 H), 1.29-1.45 (m, 1 H), 1.64 (d, J = 13.2Hz, 2 H), 1.92 (t, J = 10.4 Hz, 2 H), 2.57-2.70 (m, 1 H), 2.95 (s, 3 H),3.19-3.27 (m, 2 H), 3.54-3.68 (m, 2 H), 3.68-3.82 (m, 2.5 H), 2.88 (d, J= 7.1 Hz, 2.5 H), 4.15 (t, J = 8.0 Hz, 1 H), 7.63- 7.70 (m, 1 H),7.71-7.83 (m, 3 H), 7.91 (d, J = 8.2 Hz, 2 H), 8.16 (br. s., 2 H), 13.18(br. s., 1 H) MS m/z 561 (M + H)+ 764

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cycloprropylcarbonyl)azetidin-3-yl]methyl}-8-(trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹HNMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.77 (m, 2 H), 0.91 (br. s., 2H), 1.26 (br. s., 3 H), 1.96-2.16 (m, 2 H), 2.64-2.88 (m, 1 H),3.53-3.70 (m, 2 H), 3.71-4.12 (m, 6 H), 4.20 (t, J = 7.7 Hz, 1 H), 4.46(d, J = 13.3 Hz, 1 H), 6.86 (s, 1 H), 7.52-7.73 (m, 5 H), 7.76-7.92 (m,3 H) MS m/z 579 (M + H)+ 765

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8-(trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62-0.77 (m, 2 H), 0.87-0.97 (m, 2 H), 1.24-1.34(m, 2 H), 1.97-2.15 (m, 3 H), 2.67-2.86 (m, 1 H), 3.54-3.68 (m, 2 H),3.74-4.12 (m, 6 H), 4.20 (t, J = 8.0 Hz, 1 H), 4.46 (d, J = 13.3 Hz, 1H), 6.65 (br. s., 1 H), 7.30 (t, J = 2.7 Hz, 1 H), 7.43- 7.55 (m, 2 H),7.64 (d, J = 8.2 Hz, 2 H), 7.83 (d, J = 8.1 Hz, 2 H), 7.92 (s, 1 H),8.40 (br. s., 1 H) MS m/z 578 (M + H)+ 766

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8-(trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.57-0.69 (m, 2 H), 0.78-0.88 (m, 2 H), 1.59 (d, J =13.5 Hz, 3 H), 1.90-2.08 (m, 2 H), 2.71 (br. s., 1 H), 3.46-3.60 (m, 2H), 3.67-4.05 (m, 6 H), 4.14 (t, J = 7.8 Hz, 1 H), 4.38 (d, J = 13.5 Hz,1 H), 7.189 (s, 2 H), 7.46-7.67 (m, 4 H), 7.73 (d, J = 8.0 Hz, 2 H),7.93 (s, 1 H) MS m/z 579 (M + H)+ 767

3-{[1-(Cycloprropylcarbonyl)azetidin-3-yl]methyl}-8-(2-methylpropanoyl)-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm0.56-0.70 (m, 4 H), 1.03 (br. s., 6 H), 1.23 (s, 1 H), 1.30-1.42 (m, 1H), 1.45- 1.59 (m, 2 H), 1.62-1.85 (m, 2 H), 2.61 (m, J = 5.5 Hz, 1 H),2.86-3.02 (m, 1 H), 3.09-3.26 (m, 2 H), 3.46-3.62 (m, 1 H), 3.65-3.81(m, 2 H), 3.86 (br. s., 1 H), 3.88 (s, 3 H), 3.97 (d, J = 12.1 Hz, 1 H),4.10-4.19 (m, 1 H), 4.23-4.37 (m, 1 H), 7.66-7.73 (m, 2 H), 7.77 (d, J =9.9 Hz, 4 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.94 (s, 1 H), 8.22 (s, 1 H) MSm/z 593 (M + H)+ 768

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(N,N-dimethylglycyl)-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δppm 0.51-0.71 (m, 2 H), 0.82 (br. s., 2 H), 1.06-1.31 (m, 3 H),1.40-1.68 (m, 2 H), 1.77-2.05 (m, 3 H), 2.46 (br. s., 6 H), 2.67 (br.s., 1 H), 3.24-3.55 (m, 4 H), 3.55-3.72 (m, 1 H), 3.72-3.87 (m, 3 H),3.90 (br. s., 3 H), 4.02-4.20 (m, 1 H), 4.25-4.51 (m, 1 H), 7.19 (s, 1H), 7.45- 7.65 (m, 5 H), 7.65-7.84 (m, 3 H) MS m/z 608 (M + H)+ 769

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-8-(methylsulfonyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.88(m, 4 H), 1.09 (t, J = 6.8 Hz, 1 H), 1.18-1.30 (m, 1 H), 1.30-1.48 (m, 1H), 1.63 (d, J = 12.5 Hz, 2 H), 1.91 (t, J = 10.2 Hz, 2 H), 2.55-2.74(m, 1 H), 2.95 (s, 2 H), 3.08-3.28 (m, 3 H), 3.35- 3.44 (m, 3 H),3.50-3.66 (m, 2 H), 3.67- 3.84 (m, 2 H), 3.83-3.86 (m, 2 H), 3.88 (s, 3H), 4.15 (t, J = 8.2 Hz, 1 H), 7.66- 7.73 (m, 2 H), 7.77 (d, J = 7.6 Hz,4 H), 7.83-7.99 (m, 3 H), 8.22 (s, 1 H) MS m/z 601 (M + H)+ 770

8-(Cyclopropylcarbonyl)-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz,DMSO-d₆) δ ppm 0.53-0.67 (m, 4 H), 0.67-0.83 (m, 4 H), 1.23 (br. s., 1H), 1.29-1.43 (m, 1 H), 1.43-1.63 (m, 2 H), 1.63-1.76 (m, 1 H),1.76-1.92 (m, 1 H), 1.92-2.15 (m, 1 H), 2.54-2.69 (m, 1 H), 3.12-3.27(m, 2 H), 3.52-3.79 (m, 3 H), 3.79-3.86 (m, 1 H), 3.88 (s, 3 H), 4.14(t, J = 7.0 Hz, 1 H), 4.20- 4.37 (m, 2 H), 7.70 (m, J = 8.0 Hz, 2 H),7.76 (d, J = 10.0 Hz, 4 H), 7.85-7.96 (m, 3 H), 8.22 (s, 1 H) MS m/z 591(M + H)+ 771

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(1-methylethyl)-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δppm 0.56-0.68 (m, 2 H), 0.75-0.89 (m, 2 H), 1.01-1.28 (m, 6 H),1.49-1.88 (m, 5 H), 2.03-2.29 (m, 2 H), 2.67 (dt, J = 13.4, 6.6 Hz, 1H), 2.83-3.20 (m, 4 H), 3.47 (dd, J = 9.1, 5.8 Hz, 1 H), 3.71-3.88 (m, 3H), 3.90 (s, 3 H), 4.11 (t, J = 7.9 Hz, 1 H), 7.19 (s, 1 H), 7.48-7.63(m, 6 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.74 (s, 1 H) MS m/z 565 (M + H)+772

3-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δppm 0.54-0.68 (m, 2 H), 0.75-0.88 (m, 2 H), 1.56 (d, J = 13.3 Hz, 2 H),1.76-2.15 (m, 6 H), 2.59-2.71 (m, 2 H), 2.78 (t, J = 10.6 Hz, 2 H),2.86-3.02 (m, 2 H), 3.63 (t, J = 4.7 Hz, 2 H), 3.71-3.88 (m, 3 H), 3.90(s, 3 H), 4.11 (t, J = 8.1 Hz, 1 H), 7.19 (s, 1 H), 7.47-7.63 (m, 6 H),7.69 (d, J = 8.1 Hz, 2 H), 7.74 (s, 1 H) MS m/z 567 (M + H)+ 829

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(2-(4-methylpiperazin-1- yl)pyridin-4-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 541.3 (M + H)+ 828

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(2-(piperazin-1-yl)pyridin-4-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en- 4-one MS m/z 527.2 (M + H)+822

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-methyl-4-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 528.3 (M + H)+ 845

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(1H-dinol-5-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.66-0.79 (m, 2 H), 0.89-1.01 (m, 2 H), 1.45-1.55(m, 1.5 H), 1.58-1.68 (m, 1.5 H), 1.80-1.91 (m, 0.5 H), 1.94- 2.03 (m, 4H), 2.06-2.17 (m, 4 H), 2.35- 2.46 (m, 0.5 H), 2.46-2.58 (m, 0.5 H),3.01 (dd, J = 12.1, 7.1 Hz, 0.5 H), 3.16- 3.24 (m, 0.5 H), 3.31 (dt, J =11.6, 8.1 Hz, 0.5 H), 3.49-3.58 (m, 2 H), 3.62-3.70 (m, 2 H), 6.66 (br.s., 1 H), 7.31 (d, J = 3.0 Hz, 1 H), 7.42-7.54 (m, 3 H), 7.60 (d, J =5.1 Hz, 2 H), 7.91 (s, 1 H), 8.46 (br. s., 1 H). MS m/z 499.2 (M + H)+805

5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-6-((1-nicotinoylazetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 505.2 (M + H)+ 796

6-((1-(1- hydroxycyclobutanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498.3 (M + H)+ 851

(R)-5-(4-(1H-indol-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 467 (M + H)+ 823

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 820

(R)-5-(3″-chloro-[1,1′:4′,1″-terphenyl]-4-yl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 538 (M + H)+ 821

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4″-methyl-[1,1′:4′,1″-terphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 518 (M + H)+848

(R)-4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl-3-carboxylic acid MS m/z 458 (M + H)+ 819

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 818

(S)-5-(4-(benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 817

(S)-5-(4-(benzo[b]thiophen-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484 (M + H)+ 843

(S)-5-(4-(1H-indol-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 467 (M + H)+ 816

(S)-5-(4-(1H-indazol-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 815

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 813

(S)-5-(3″-chloro-[1,1′:4′,1″-tertphenyl]-4-yl)-6-((1-(cyclopropanecarbonyl)piperidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 538 (M + H)+ 812

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4″-methyl[1,1′:4′,1″-terphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 518 (M + H)+811

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-isopropyl-2H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 496 (M + H)+ 809

(R)-7-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-3,4-dihydroquinolin- 2(1H)-one MS m/z 483 (M + H)+ 802

(R)-5-(4-(5-chlorppyridin-3-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 449 (M + H)+ 849

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-methyl-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 850

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(3-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 814

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-3-methylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 827

6-((1-cyclopropanecarbonyl)piperidin-4-yl)methyl)-5-(4″-methyl-(1-methyl-1H-pyrazol-4-yl)-[1,1′:4′,1″-terphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MSm/z 584 (M + H)+ 836

5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-methylphenyl)-1-methyl-1H- indazole-3-carbonitrile MS m/z493 (M + H)+ 847

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2,3-dimethylbenzofuran-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)+ 846

6-((1-cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(2,3-dimethylbenzofuran-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 806

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-morpholinopyridin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 486 (M + H)+ 807

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(1-isopropyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 808

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(2-isopropyl-2H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 803

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(1-cyclopropyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 480 (M + H)+ 804

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(1-(cyclopropylmethyl)- 1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 494 (M + H)+ 801

5-(4-(1,5-naphthyridin-3-yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl),4-6diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 800

1-(5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)pyridin-2-yl)cyclopropanecarbonitrile MS m/z 466 (M + H)+ 797

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-(2-hydroxypropan-2- yl)pyridin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 794

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(5-(2-hydroxypropan-2- yl)pyridin-2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 798

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-cyclopropylpyridin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 441 (M + H)+ 842

3-(5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2H-indazol-2- yl)propanenitrile MS m/z 493 (M + H)+792

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-methyl-1H-pyrazolo[4,3-b]pyridin-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 455 (M + H)+ 795

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-propylpyridin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 443 (M + H)+ 838

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4′-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-oneMS m/z 522 (M + H)+ 789

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-(oxetan-3-yl)- 1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 514 (M + H)+ 788

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(1-(oxetan-3-yl)-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 777

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(3-fluoro-3′-(methylsulfonyl)- [1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 775

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-methyl-3′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 492 (M + H)+ 776

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(3′-(isopropylsulfonyl)-3-methyl-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z520 (M + H)+ 841

5-(4-(7-bromoquinolin-2-yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 529 (M + H)+ 839

5-(4-(7-bromo-3-methylquinolin-2- yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 840

7-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)quinolin-2(1H)-oneMS m/z 467 (M + H)+ 793

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 791

5-(4-(7-bromo-4-methylquinolin-2- yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 790

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(2-methy7lquinolin-5-yl)phenyl)-4,6-diazaspiro[2.4]jept-4-en-7- one MS m/z 465 (M + H)+ 787

5-(4-(7-bromo-3-methylquinolin-2-yl)-2- methylphenyl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 571 (M + H)+ 786

5-(4′-(1-(cyclopropylmethyl)-1H-pyrazol-5-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopeopanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 548 (M + H)+ 785

5-(4′-(1-isobutyl-1H-p[yrazol-5-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1-methylcyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 550 (M + H)+ 784

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(4-(6-isopropylpyridin-3-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 443 (M + H)+ 844

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(5-(1-methyl-1H-indazol-5-yl)pyrazin)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 443 (M + H)+ 799

5-(4-(1,8-baphthyridin-3-yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 837

5-(2-fluoro-4-(1-(2-hydroxyethyl)-1H- indazol-5-yl)phenyl)-6-((1-(1-hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 518 (M + H)+ 834

5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-1-methyl-1H- indazole-3-carbonitrile MS m/z497 (M + H)+ 783

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 515 (M + H)+ 778

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 529 (M + H)+ 782

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 525 (M + H)+ 779

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 511 (M + H)+ 780

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 547 (M + H)+ 781

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N-methylcyclopropanecarboxamide MS m/z 551 (M + H)+ 855

(R)-2-(4-(5-chloropyridin-3-yl)-2- methylphenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-rn-4- one MS m/z 491.2 (M + H)+ 867

(R)-5-(4-(5-aminopyridi9n-3-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 859

6-((1-(cyclopropanecarbonyl)piperidin-4-yl)methyl)-5-(4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 496 (M + H)+868

5-(4-benzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.62 (dd, J = 7.4, 3.3 Hz, 2 H), 0.76- 0.89 (m, 2H), 1.21 (td, J = 7.9, 4.1 Hz, 1 H), 1.69-1.79 (m, 2 H), 1.79-1.91 (m, 2H), 2.66-2.85 (m, 1 H), 3.48 (dd, J = 9.7, 5.7 Hz, 1 H), 3.63-3.77 (m, 1H), 3.78- 3.98 (m, 3 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.39 (t, J = 7.5 Hz,1 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.89 (d, J =7.8 Hz, 1 H), 7.92-8.01 (m, 2 H), 8.05 (d, J = 8.1 Hz, 1 H). MS m/z541.3 (M + H)+ 869

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.51-0.66 (m, 2 H), 0.77-0.87 (m, 2 H), 1.18-1.27(m, 1 H), 1.66-1.76 (m, 2 H), 1.76-1.86 (m, 2 H), 2.42 (s, 3 H),2.69-2.88 (m, 1 H), 3.47-3.58 (m, 1 H), 3.68-3.80 (m, 1 H), 3.80-3.91(m, 2 H), 3.94 (s, 1 H), 4.16 (t, J = 8.3 Hz, 1 H), 6.23 (s, 1 H), 7.30(s, 2 H), 7.37-7.56 (m, 3 H), 7.70 (s, 1 H), 7.97 (br. s., 1 H). MS m/z541.3 (M + H)+ 870

6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methy7l-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz,CHLOROFORM-d) δ ppm 0.60 (br. s., 2 H), 0.81 (br. s., 2 H), 1.21 (br.s., 1 H), 1.72 (br. s., 2 H), 1.80 (br. s., 2 H), 2.67-2.90 (m, 1 H),3.43- 3.59 (m, 1 H), 3.71 (br. s., 1 H), 3.77 (s, 3 H), 3.83 (d, J = 8.2Hz, 3 H), 4.16 (br. s., 1 H), 6.49 (br. s., 1 H), 6.98-7.12 (m, 1 H),7.28-7.61 (m, 5 H), 7.81 (br. s., 1 H). MS m/z 527.2 (M + H)+ 871

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.64-0.76 (m, 2 H), 0.85-0.99 (m, 2 H), 1.42-1.55 (m, 1.5 H), 1.59-1.73(m, 0.5 H), 1.76-1.84 (m, 2 H), 1.86- 1.92 (m, 2 H), 1.94-2.06 (m, 1 H),2.35- 2.51 (m, 1 H), 2.99 (dd, J = 12.0, 7.3 Hz, 0.5 H), 3.16-3.38 (m, 1H), 3.44-3.68 (m, 3 H), 3.68-3.76 (m, 1.5 H), 4.13 (s, 3 H), 7.43-7.55(m, 2 H), 7.55-7.70 (m, 3 H), 7.98 (s, 1 H), 8.07 (s, 1 H). MS m/z 509.9(M + H)+ 872

6-(3-fluoro-4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm0.85 (br. s., 2 H), 1.15 (d, J = 7.0 Hz, 2 H), 1.67-1.78 (m, 2 H),1.78-1.89 (m, 2 H), 2.37 (br. s., 1 H), 2.77 (br. s., 1 H), 3.57 (br.s., 1 H), 3.71-3.88 (m, 2 H), 4.00 (br. s., 2 H), 4.35 (br. s., 1 H),7.52 (d, J = 10.7 Hz, 1 H), 7.56-7.66 (m, 3 H), 7.76-7.84 (m, 1 H),7.90-8.00 (m, 2 H), 8.06 (s, 1 H), 8.22 (s, 1 H). MS m/z 509 (M + H)+873

(R)-2-(4-(1H-indol-6-yl)-2-methylphenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.87-1.02 (m, 2 H), 1.44-1.55(m, 1.5 H), 1.60-1.68 (m, 1.5 H), 1.68 (br. s., 0.5 H), 1.93- 2.05 (m, 4H), 2.06-2.20 (m, 4 H), 2.42 (s, 3 H), 2.44-2.52 (m, 0.5 H), 3.01 (dd, J= 11.9, 6.8 Hz, 0.5 H), 3.13-3.23 (m, 0.5 H), 3.27-3.44 (m, 1 H),3.46-3.70 (m, 4 H), 6.60 (br. s., 1 H), 7.29 (d, J = 4.0 Hz, 1 H),7.34-7.44 (m, 2 H), 7.53-7.64 (m, 3 H), 77.3 (dd, J = 8.3, 3.3 Hz, 1 H),8.64 (s, 0.5 H), 8.62 (s, 0.5 H). MS m/z 595.3 (M + H)+ 874

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(1H-indol-6-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.63-0.77 (m, 2 H), 0.83-0.96 (m, 2 H), 1.35-1.49(m, 1.5 H), 1.56 (dd, J = 12.6, 7.6 Hz, 0.5 H), 1.78-1.89 (m, 0.5 H),1.89-2.08 (m, 5 H), 2.14 (br. s., 4 H), 2.30-2.45 (m, 0.5 H), 2.45-2.59(m, 0.5 H), 2.97 (dd, J = 12.4, 7.3 Hz, 0.5 H), 3.17 (t, J = 8.8 Hz, 0.5H), 3.28 (d, J = 11.6 Hz, 0.5 H), 3.42-3.54 (m, 1.5 H), 3.60-3.74 (m,2.5 H), 6.53 (br. s., 1 H), 7.25 (br. s., 1 H), 7.29 (d, J = 8.6 Hz, 1H), 7.48 (s, 0.5 H), 7.45 (s, 0.5 H), 7.58 (br. s., 2 H), 7.63- 7.72 (m,2 H), 8.41 (br. s., 1 H) MS m/z 499.2 (M + H)+ 875

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(quinolin-7-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.65-0.78 (m, 2 H), 0.87-1.02 (m, 2 H), 1.44-1.56(m, 1.5 H), 1.58-1.71 (m, 0.5 H), 1.80-1.91 (m, 1 H), 1.95- 2.13 (m, 8H), 2.41 (dt, J = 14.4, 7.5 Hz, 0.5 H), 2.47-2.59 (m, 0.5 H), 3.00 (dd,J = 11.9, 7.3 Hz, 0.5 H), 3.19-3.27 (m, 0.5 H), 3.32 (dt, J = 12.0, 7.9Hz, 0.5 H), 3.48- 3.59 (m, 2 H), 3.60-3.72 (m, 2.5 H), 7.49 (dd, J =8.1, 4.0 Hz, 1 H), 7.57-7.65 (m, 1 H), 7.65-7.76 (m, 2 H), 7.81-7.87 (m,1 H), 7.98 (d, J = 8.6 Hz, 1 H), 8.25 (d, J = 8.1 Hz, 1 H), 8.39 (s, 1H), 8.94-9.10 (m, 1 H). MS m/z 511.2 (M + H)+ 876

(R)-2-(4-(benzo[b]thiophen-5-yl)-2- fluorophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro{4.4[non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.64-0.77 (m, 2 H), 0.91 (br. s., 2 H), 1.39-1.48(m, 1.5 H), 1.56 (dd, J = 12.9, 7.8 Hz, 0.5 H), 1.78-1.88 (m, 0.5 H),1.90-2.06 (m, 4.5 H), 2.13 (br. s., 4 H), 2.31-2.41 (m, 0.5 H),2.42-2.57 (m, 0.5 H), 2.97 (dd, J = 12.1, 7.6 Hz, 0.5 H), 3.13-3.21 (m,0.5 H), 3.22-3.33 (m, 0.5 H), 3.44-3.54 (m, 1.5 H), 3.55-3.72 (m, 3 H),7.35 (d, J = 5.1 Hz, 1 H), 7.45-7.54 (m, 3 H), 7.61 (d, J = 7.1 Hz, 1H), 7.68- 7.77 (m, 1 H), 7.92 (d, J = 8.6 Hz, 1 H), 8.00 (s, 1 H). MSm/z 516.2 (M + H)+ 877

(R)-2-(4-(1H-benzo[d]imidazol-5-yl)-21- fluorophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.60-0.72 (m, 2 H), 0.78-0.93 (m, 2 H), 1.31-1.49(m, 1.5 H), 1.57 (dd, J = 12.6, 8.1 Hz, 0.5 H), 1.76 (dd, J = 10.9, 5.3Hz, 0.5 H), 1.82-2.07 (m, 8.5 H), 2.23-2.38 (m, 0.5 H), 2.38-2.51 (m,0.5 H), 2.89 (dd, J = 11.9, 7.3 Hz, 0.5 H), 3.10- 3.27 (m, 1 H),3.37=3.49 (m, 2 H), 3.50- 3.63 (m, 2.5 H), 7.30-7.53 (m, 4 H), 7.58-7.70(m, 2 H), 8.06 (s, 1 H). MS m/z 500.2 (M + H)+ 878

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1- (1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en- 4-one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.90-1.01 (m, 2 H), 1.17 (br. s., 2 H), 1.51 (br.s., 0.5 H), 1.65 (br. s., 0.5 H), 1.90-2.11 (m, 5 H), 2.14-2.33 (m, 4H), 2.49 (br. s., 1 H), 3.09 (br. s., 0.5 H), 3.44 (br. ., 0.5 H), 3.50(s, 1.5 H), 3.72 (br. s., 0.5 H), 3.92 (d, J = 7.3 Hz, 3 H), 6.85 (d, J= 1.5 Hz, 1 H), 7.57 (d, J = 2.0 Hz, 1 H), 7.58-7.64 (m, 1 H), 7.70 (d,J = 2.2 Hz, 1 H), 7.79-7.89 (m, 5 H). MS m/z 498.2 (M + H)+ 879

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(1H-indazol-6-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz,CHLOROFORM-d) δ ppm 0.69 (d, J = 7.6 Hz, 2 H), 0.82-0.96 (m, 2 H), 1.43(dd, J = 7.8, 4.8 Hz, 1.5 H), 1.57 (br. s., 0.5 H), 1.81 (br. s., 0.5H), 1.90-2.10 (m, 4.5 H), 2.14 (br. s., 4 H), 2.36 (br. s.,k 0.5 H),2.52 (br. s., 0.5 H), 2.86-2.97 (m, 0.5 H), 3.18 (t, J = 8.6 Hz, 0.5 H),3.23-3.34 (m, 0.5 H), 3.39-3.56 (m, 2 H), 3.58 (br. s., 1 H), 3.64 (br.s., 1.5 H), 7.28 (d, J = 8.1 Hz, 1 H), 7.36- 7.49 (m, 2 H), 7.61-7.75(m,l 2 H), 7.79 (d, J = 8.1 Hz, 1 H), 8.11 (s, 1 H). MS m/z 500.1 (M +H)+ 880

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm0.65-0.76 (m, 2 H), 0.84-0.97 (m, 2 H), 1.35-1.49 (m, 1.5 H), 1.50-1.63(m, 0.5 H), 1.84 (br. s., 0.5 H), 1.91-2.05 (m, 5 H), 2.12 (br. s., 3.5H), 2.31-2.41 (m, 0.5 H), 2.50 (d, J = 7.6 Hz, 0.5 H), 2.96 (dd, J =12.1, 7.1 Hz, 0.5 H), 3.13-3.34 (m, 0.5 H), 3.43-3.54 (m, 2 ), 3.55-3.70 (m, 3 H), 4.07 (s, 3 H), 7.43-7.51 (m, 2 H), 7.59 (t, J = 9.9 Hz, 2H), 7.65- 7.74 (m, 1 H), 7.93 (s, 1 H), 8.04 (s, 1 H). MS m/z 514.21(M + H)+ 881

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(2-fluoro-4-(1H-pyrrolo[2,3- b]pyridin-5-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm0.55-0.69 (m, 2 H), 0.79-0.94 (m, 2 H), 1.31-1.48 (m, 1.5 H), 1.55 (dd,J = 12.6, 8.1 Hz, 0.5 H), 1.70-1.80 (m, 0.5 H), 1.81-2.06 (m, 8.5 H),2.25-2.36 (m, 0.5 H), 2.37-2.49 (m, 0.5 H), 2.88 (dd, J = 11.9, 7.3 Hz,0.5 H), 3.07-3.17 (m, 0.5 H), 3.22 (dt, J = 11.5, 8.1 Hz, 0.5 H), 3.36-3.49 (m, 2 H), 3.50-3.64 (m, 2.5 H), 6.55 (d, J = 3.5 Hz, 1 H),7.33-7.44 (m, 2 H), 7.46-7.59 (m, 2 H), 8.12 (s, 1 H), 8.49 (br. s., 1H), 9.63 (s, 0.5 H), 9.59 (s, 0.5 H). MS m/z 500.3 (M + H)+ 882

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(3-methyl-4′-(5-methyl-1,3,4-oxadiazol-2-yl)-[1,1′-biphenyl]-4-yl)-1,3- diazaspiro[4.4]non-1-en-4-oneMS m/z 538.2 (M + H)+ 883

(R)-2-(4-(benzo[d][1,3]dioxol-5-yl)-2- methylphenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 500.3 (M + H)+ 884

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(2,3-dihydrobenzofuran-5- yl)-2-methylphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 498.2 (M + H)+ 885

(R)-5-(4-(3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methuyl)-4-oxo-1,3-diazaspiro[4.4]non- 1-en-2-yl)-3-fluorophenyl)-1H-benzo[d]imidazol-2(3H)-one MS m/z 516.2 (M + H)+ 886

(R)-2-(4′-acetyl-3-fluoro-[1,1′-biphenyl]-4- yl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 502.2 (M + H)+ 887

5-(4-(5-bromopyridin-2-yl)phenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 479 (M + H)+ 888

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 494.1 (M + H)+ 889

(S)-methyl 3-((2-(4-(benzofuran-5- yl)phenyl)-4-oxo-8-oxa-1,3-diazaspiro[4.5]dec-1-en-3- yl)methyl)pyrrolidin-1-carboxylate MS m/z488.1 (M + H)+ 890

(R)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 540.2 (M + H)+ 891

(S)-methyl 6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-7-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-8-oxo-2,5,7-triazaspiro]3.4[ovt-5-ene-2- carboxylate MS m/z 577.3 (M + H)+892

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-(((R)-1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazxaspiro[4.4]non- 1-en-4-one MS m/z 541.1 (M +H)+ 893

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 552.3 (M + H)+ 894

(3S)-methyl 3-((2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidin-1-carboxylate MSm/z 514.2 (M + H)+ 895

2-(4-(quinolin-7-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 509.1 (M + H)+ 896

3-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 505.2 (M + H)+ 897

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 498.2 (M + H)+ 898

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 480.2 (M + H)+ 899

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 538.2 (M + H)+ 900

(S)-methyl 7-((1- (methylsulfionyl)pyrrolidin-3-yl)methyl)-8-oxo-6-(4-(quinolin-7-yl)phenyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 548.2 (M + H)+ 901

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-3-((1-(thiazol-2-carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-oneMS m/z 553.2 (M + H)+ 902

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 508.1 (M + H)+ 903

methyl 3-((4-oxo-2-(4-(quinolin-7-yl)phenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 471.2 (M + H)+ 904

methyl 3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)azetidin-1-carboxylate MS m/z 460.2 (M + H)+ 905

methyl 3-((2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z474.3 (M + H)+ 906

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)-6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-8-oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 557.2 (M + H)+ 907

(R)-methyl 6-(4-(1-methyl-1H-indazol-5- yl)phenyl)-8-oxo-7-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 569.1 (M + H)+ 908

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 541.1 (M +H)+ 909

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 527.1 (M +H)+ 910

2-(4-(quinolin-7-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 523.2 (M + H)+ 911

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-oneMS m/z 567.2 (M + H)+ 912

3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 505.2 (M + H)+ 913

(S)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 508.1 (M + H)+ 914

2-(4-(benzofuran-5-yl)phenyl)-3-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 494.1 (M + H)+ 915

(3S)-methyl 3-((2-(4-(1-methyl-1H- indazol-5-yl)phenyl)-4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidin-1-carboxylate MS m/z488.2 (M + H)+ 916

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)-6-(4-(1-methyl-1H-indazol-5-yl)phenyl)-8-oxo-5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 531.2 (M + H)+917

(S)-methyl 6-(4-(1-methyl-1H-indazol-5-yl)phenyl)-7-((1-(methylsulfonyl)pyrrolidin- 3-yl)methyl)-8-oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 551.3 (M + H)+ 918

(S)-2-(4′-(1-metrhyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 548.3 (M + H)+ 919

(R)-methyl 6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 595.1 (M + H)+ 920

2-(4-(quinolin-7-yl)phenyl)-3-(((R)-1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 538.1 (M +H)+ 921

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 534.2 (M + H)+ 922

methyl 3-((4-oxo-2-(4-(quinolin-7-yl)phenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 485.2 (M + H)+ 923

(R)-methyl 6-(4-(1-methyl-1H-indazol-5-yl)phenyl)-8-oxo-7-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 584.2 (M + H)+ 924

(S)-methyl 6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1-(pyrrolidine-1-carbonyl)pyrrolidin-3-yl)metrhyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 596.3(M + H)+ 925

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)+ 926

(S)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(methylsulfonyl)pyrrolidin- 3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 522.1 (M + H)+ 927

methyl 3-((2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4-oxo-7-oxa-1,3- diazaspiro[4.4]non-1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 500.2 (M + H)+ 928

methyl 3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-8-oxa-1,3-diazaspiro[4.5]dec-1-en- 3-yl)azetidine-1-carboxylate MSm/z 474.2 (M + H)+ 929

(R)-methyl 6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 610.1(M + H)+ 930

2-(4-(quinolin-7-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 524.1 (M + H)+ 931

(S)-methyl 6-(4-(benzofuran-5-yl)phenyl)-7-((1-(methoxycarbonyl)pyrrolidin-3-yl)methyl)-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z517.1 (M + H)+ 932

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 513.1 (M + H)+ 933

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-(((S)-1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 508.1 (M +H)+ 934

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 527.1 (M +H)+ 935

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 526.2 (M +H)+ 936

methyl 3-((2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4-oxo-8-oxa-1,3- diazaspiro[4.5]dec-1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 514.2 (M + H)+ 937

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 512.3 (M +H)+ 938

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 512.2 (M +H)+ 939

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 534.2 (M + H)+ 940

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 552.2 (M + H)+ 941

methyl 3-((2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4-oxo-8-oxa-1,3-diazaspiro[4.5]dec-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z488.2 (M + H)+ 942

3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-2-(4-(quinolin7-yl)phenyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 491.2 (M + H)+ 943

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-3-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 567.2 (M + H)+ 944

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 494.2 (M + H)+ 945

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-((1-(pyrrolidine-1-carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 513.3 (M +H)+ 946

(R)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 8-oxo-7-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 555.1 (M + H)+ 947

2-(4-(quinolin-7-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-ene-4-one MS m/z 538.1 (M + H)+ 948

(R)-2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-3-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 581.2 (M + H)+ 949

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(thiazole-2-carbonyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 527.2 (M + H)+ 950

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(methylsulfonyl)azetidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 520.2 (M + H)+ 951

3-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-8-isopropyl-2-(4-(isoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en- 4-one MS m/z 536 (M + H)+ 952

3-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-8-(2,2,2-trifluoroacetyl)-2-(4-(1-(2,2,2-trifluoroacetyl)-1H-indol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en- 4-one MS m/z 578 (M + H)+ 953

(S)-methyl 3-((2-(4-(1-methyl-1H-indazol- 5-yl)phenyl)-4-oxo-8-oxa-1,3-diazaspiro[4.5]dec-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z502.2 (M + H)+ 954

(3S)-methyl 3-((2-(4-(benzofuran-5- yl)phenyl)-4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 474.2 (M + H)+ 955

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3-(((R)-1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 526.1 (M +H)+ 956

(S)-methyl 6-(4-(benzofuran-5-yl)phenyl)-7-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z537.1 (M + H)+ 957

(R)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 8-oxo-7-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 570.2 (M + H)+ 958

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 541.1 (M +H)+ 959

(R)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-3-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 555.1 (M + H)+ 960

(S)-3-((1-(methylsulfonyl)pyrrolidin-3-yl)methyl)-2-(4-quinolin-7-yl)phenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 519.2 (M + H)+ 961

2-(4-(benzofuran-5-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 512.2 (M + H)+ 962

(R)-methyl 8-oxo-6-(4-(quinolin-7- yl)phenyl)-7-((1-(thiazole-2-carbonyl)pyrrolidin-3-yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 581.1 (M + H)+ 963

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)-8-oxo-6-(4-(quinolin-7-yl)phenyl)-2,5,7-triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 528.3 (M + H)+ 964

3-((1-(cyclopropanec arbonyl)azetidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-8-(2,2,2,-trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 593 (M + H)+ 965

(R)-2-(4-(quinolin-7-yl)phenyl)-3-((1-(2,2,2-trifluoroacetyl)pyrrolidin-3-yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 537.2 (M +H)+ 966

(R)-2-(4-(1H-indazol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 541 (M + H)+ 967

(R)-2-(4-(1H-indol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-8-(2-hydroxyethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 540 (M + H)+ 968

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-(2,2,2-trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 593 (M + H)+ 969

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)+ 970

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MSm/z 589 (M + H)+

BIOLOGICAL EXAMPLES Biological Example 1 Fatty Acid Synthase (FASN)Inhibition Scintillation Proximity Assay

In this assay, inhibition of FASN activity is measured using³H-acetyl-CoA and malonyl-CoA as substrates. ³H-Acetyl CoA is convertedto ³H-palmitate through a series of reactions by the FASN protein, whichcontains 7 functional domains and carries out 7 enzymatic reactions toultimately produce ³H-palmitate. The assay principle is based upon thefact that ³H-acetyl-CoA is hydrophilic and the end product, ³H-palmitateis hydrophobic. The hydrophobic ³H-palmitate binds to scintillationproximity assay (SPA) imaging beads (resulting in light emission fromthe imaging beads) whereas the hydrophilic ³H-acetyl-CoA does not bindto the imaging beads (and therefore does not result in light emissionfrom the imaging beads).

10 μL assay buffer (100 mM KH₂PO₄ pH 7.5, 1 mM DTT) (20 μL in blanks)was added to a 384-well white optiplate plate (Perkin Elmer). 0.9 μLtest compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM,0.10 μM, 0.03 μM and 0.01 μM)/DMSO and 10 μL hFASN enzyme (full length,300 ng, purified in house) or 10 μL assay buffer was added to the wells.Then 10 μL 450 μM NADPH (Sigma N7505), 18.75 μM [³H]-acetyl-CoA (PerkinElmer NET-290L), 150 μM malonyl-CoA (Sigma M4263) were added, mixed andincubated at room temperature for 60 minutes. The reaction was stoppedby adding 20 μL Streptavidin coupled imaging beads (25 mg/ml). Afterincubation for 30 minutes at room temperature in the dark, the 384 wellplate was centrifuged at 1500 rpm for 3 minutes and was measured afterat least 24 hrs by the LEADseeker™, measuring emission using a 610±20 nmpass filter. (Bays, N. W., et al., “A simplified scintillation proximityassay for fatty acid synthase activity: development and comparison withother FAS activity assays”, J. Biomol. Screen., 2009, pp 636-642, Vol.14(6).)

Raw data generated by the instrument were normalized to % Controlminvalues, which were calculated as:% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and highcontrol wells on the plate, after manual exclusion of outliers. A plotof Controlmin versus test compound concentration was fitted to a4-parameter logistic curve using a non-linear least squares regressionmethod. From the plot, an IC₅₀ (concentration at such 50% inhibition isachieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀),when IC₅₀ is expressed in molar units.

Representative compounds of formula (l) the present invention weretested according to the procedure as described in Biological Example 1above, with results as listed in Table 6, below. Wherein the resultslisted below, the pIC₅₀ value is preceded with a “˜”, the “˜” indicatesthat the standard error of the pIC₅₀ value, as estimated by thenon-linear regression algorithm, is larger than 0.5. This corresponds toa factor of uncertainly on the IC₅₀ that is larger than square root of10 (>3.162).

TABLE 6 FASN pIC50 Human FASN Human FASN ID No. pIC₅₀ % inhibition @ 10μM 1 6.24 93 2 7.34 108.6 3 <5 44.3 4 7.47 102.6 5 5.67 74.6 6 5.14 61.67 <5 33.7 8 <5 5.1 9 <5 11.4 10 6.69 89.7 11 6.03 82.2 12 7.59 99.4 13<5 29.7 14 6.83 98.2 15 7.36 113 16 5.86 72.5 17 6.64 97 18 <5 42.7 195.86 78 20 6.8 101 22 5.97 85 24 5.73 76.4 25 ~5.31 64.4 27 7.15 100.128 7.53 109.6 29 6.03 81.7 30 7.24 107.5 31 7.66 106.7 32 <5 6.8 33 7.59109.4 34 6.93 101.7 35 7.08 106.8 36 6.26 96.2 37 <5 28.6 38 6.57 94.939 7.19 103 40 7.73 105.6 41 6.34 92.6 42 <5 23.5 43 ~5 45.4 44 <5 −0.9747 7.69 102.6 48 7.01 107.6 49 7.22 101.4 50 5.46 64.8 51 7.1 101.9 526.12 89.9 53 5.71 78.6 54 5.33 64.7 55 <5 32.7 56 6.39 89.2 57 6.12 88.158 7.6 107.7 59 7.38 98.7 60 7.03 99.4 61 5.4 63.2 62 <5 29.3 63 7.13115 64 6.15 92.9 65 7.55 101.1 66 7.13 106.5 67 6.55 100.1 68 7.2 107 696.65 100.1 70 6.27 92.5 71 7.38 102 72 7.32 106.3 73 7.48 111.1 74 7.65113.7 75 6.29 92.7 76 6.89 99.2 77 6.76 102.6 78 7.23 111.3 79 7.21107.5 80 6.36 92.1 81 7.04 109.4 82 6.67 105.2 83 5.32 65.6 84 6.0 89.285 6.45 97.9 90 6.51 101 91 <5 21.3 92 7.29 111.3 93 7.12 115.8 94 6.84110.8 95 <5 24.4 96 5.3 71.2 97 5.25 58.7 98 <5 35.1 99 5.33 61.4 1007.13 110.2 101 7.09 112.1 102 6.68 106.6 103 7.17 108.6 104 5.49 71.7105 7.0 104.1 106 6.95 109.9 107 <5 10.6 108 5.82 83.8 109 5.29 62.1 110<5 32.6 111 5.36 62.2 112 7.3 104.2 113 6.93 109.4 114 7.12 106.9 1157.52 113 116 7.55 121.2 117 6.69 107.7 118 6.45 101.1 119 6.76 107.4 1207.41 115.9 121 7.04 115.1 122 6.91 112.3 123 5.9 81.5 124 6.94 113.2 1255.4 64.6 126 6.19 96.3 127 6.31 106.7 129 5.93 90.7 130 5.42 74 131 5.0552.1 132 5.77 83.7 133 6.35 99.1 134 6.25 91.7 135 5.61 78.9 136 5.5377.7 137 6.75 111.6 138 6.41 101.5 139 6.76 111.5 140 6.65 113.9 141 6.6110.3 142 7.16 119.3 143 7.44 118.6 144 7.2 116.6 145 6.4 105.5 146 <538 147 7.15 89.5 148 6.52 104.6 150 6.98 112.9 151 6.89 111.8 152 6.91123 153 6.98 115.6 154 6.57 109.4 155 6.11 96.5 156 6.72 107.8 157 7.17112.2 158 <5 33 159 7.1 116 160 <5 29.3 161 <5 16 162 5.96 90.9 163 6.64110.5 164 7.4 115.2 165 6.64 108.3 166 5.47 71.6 167 6.28 96.4 168 6.84108 169 <5 45.7 170 5.1 55.6 171 6.67 106.6 172 6.6 107.9 173 6.42 97174 6.61 109.4 178 6.99 108 179 5.2 59.5 180 6.86 100.8 181 6.91 109.4182 6.86 103.9 183 6.86 108.8 184 6.36 106.6 186 5.81 80.4 187 6.22 96.5188 ~5 50.4 189 <5 16.7 190 6.53 105.2 191 7.1 108.3 192 6.23 94.3 2007.46 102 201 7.36 100 202 7.08 101 203 7.24 99 204 7.24 103 205 7.01 94206 7.43 101 207 7.08 101 208 7.19 99 209 7.05 108 210 7.05 103 211 7.07107 212 7.55 101 213 7.33 95 214 7.65 99 215 7.63 102 216 7.54 102 2177.54 103 218 7.14 95 219 7.12 103 220 7.04 99 221 7.01 92 222 7.56 103223 7.27 104 224 7.6 103 225 7.42 95 226 7.63 98 227 7.37 99 228 7.35103 230 7.39 107 231 7 108 232 7.08 105 233 7.3 110 234 7.68 108 2357.63 111 236 7.46 98 237 7.1 100 238 7.36 98 239 7.23 96 240 7.91 101241 7.66 100 242 7.72 103 243 7.65 104 244 7.25 101 245 7.49 98 246 7.77101 247 7.79 103 248 7.16 99 249 7.77 102 250 7.31 100 251 7.49 101 2527.57 100 253 7.45 97 254 7.53 100 255 7.2 99 256 7.27 95 257 7.31 99 2587.14 94 259 7.6 95 260 7.79 101 261 7.26 98 262 ~7.29 94 263 7.29 105264 7.43 108 265 7.34 103 266 7.47 102 267 7.58 97 268 7.26 104 269 7.65102 270 7.45 102 271 7.25 104 272 7.73 105 273 7.37 102 274 7.3 101 2787.59 113 279 7.55 107 280 7.52 109 281 7.35 114 282 7.06 106 283 7.38112 284 7.59 106 286 7.36 103 287 7.36 110 288 7.57 107 289 7.01 102 2907.1 110 291 7.56 108 292 7.06 100 293 7.42 105 294 7.37 100 295 7.27 100296 7.41 106 297 7.5 111 298 7.66 100 299 7.64 101 300 7.24 102 301 7.799 302 7.48 101 303 7.51 102 304 7.01 99 305 7.6 103 306 7.3 98 307 7.17100 308 7.32 102 309 7.7 101 310 7.4 102 311 7.6 101 312 7.12 101 3137.41 99 314 7.39 103 315 7.18 98 316 7.38 108 317 7.24 103 318 7.18 100319 7.54 105 320 7.59 102 321 7.52 99 322 7.42 102 323 7.6 101 324 7.49105 325 7.1 100 326 7.4 103 327 7.49 104 328 7.5 98 331 7.18 100 3327.73 100 333 7.26 98 334 7.66 97 335 7.19 105 336 7.3 103 337 7.44 105338 7.36 106 339 7.51 95 340 7.54 101 341 7.19 102 342 7.16 106 343 7.2998 344 7.59 99 345 7.05 99 346 7.31 97 347 7.31 98 348 7.2 96 349 7.78102 350 7.82 99 351 7.13 95 352 7.13 94 353 7.26 101 354 7.3 100 3557.52 96 356 6.99 99 357 7.4 97 358 7.51 100 359 7.4 95 361 7.4 103 3627.11 96 363 7.4 94 364 7.24 89 365 7.63 97 366 7.21 89 368 7.55 90 3697.58 102 370 7.54 100 371 7.25 101 372 7.79 101 374 7.59 99 375 7.36 103377 7.45 100 378 7.41 100 379 7.7 102 380 7.18 100 381 7.64 98 382 7.699 383 7.62 102 384 7.2 100 385 7.64 103 387 6.66 103 388 6.45 99 3895.14 56 390 6.49 99 391 6.89 104 392 6.61 91 393 ~5.54 62 394 5.97 84395 5.2 54 396 ~5.07 52 397 6.1 90 398 6.58 102 399 6.44 99 400 6.71 101401 5.43 70 402 6.86 102 404 6.75 97 405 6.89 102 406 6.9 99 407 5.63 69408 5.29 63 409 6.76 100 410 6.6 96 411 6.8 100 412 6.49 96 413 6.52 91414 6.87 101 415 5.9 80 416 ~5.75 76 417 5.28 62 418 6.82 103 419 6.2996 420 6.31 92 421 6.34 94 422 5.48 70 423 6.5 90 424 5.4 68 425 6.56 93426 6.46 94 427 6.38 91 428 6.86 101 429 6.62 96 430 5.05 52 431 6.5 97432 6.85 98 433 5.74 72 434 5.69 73 435 6.58 91 436 ~5 43 437 5.56 72438 5.48 65 439 5.02 48 440 6.71 97 441 5.4 63 442 6.7 94 443 6.04 88444 6.6 95 445 6.74 100 446 5.3 60 447 5.92 79 448 5.07 50 449 6.26 89450 6.53 98 451 5.9 82 452 6.64 97 453 6.61 94 454 ~5.22 53 455 6.79 99456 5.16 65 457 6.34 91 458 5.09 48 459 5.06 43 460 5.51 63 461 6.85 95462 6.8 98 463 6.65 93 464 5.39 66 465 6.82 99 466 6.32 87 467 6.48 93468 6.37 90 469 6.93 97 470 6.74 98 471 6.74 99 472 6.89 97 473 6.57 95474 6.91 99 475 6.78 93 476 6.58 90 477 5.51 67 478 5.86 92 479 6.79 95480 6.81 97 481 5.66 68 482 5.88 76 483 6.97 95 484 6.82 99 485 6.79 96486 5.82 81 487 5.93 81 488 6.67 88 489 6.93 97 490 6.48 81 491 6.94 100492 6.0 77 493 6.78 98 494 6.66 95 495 6.59 95 496 6.52 94 497 6.23 87498 6.94 99 499 6.61 96 500 ~5.56 74 501 5.08 52 502 6.45 94 503 5.24 58504 5.07 42 505 5.93 80 506 5.47 61 507 6.38 89 508 5.54 74 509 5.7 69510 6.02 80 511 6.45 94 512 6.17 87 513 5.91 85 514 5.13 56 515 6.74 96516 5.93 83 517 6.19 88 518 ~5.33 62 519 6.8 96 520 6.37 97 521 6.29 94522 5.78 79 523 6.29 92 524 5.68 73 525 5.98 84 526 6.04 93 527 5.8 83528 6.44 105 529 6.99 96 530 6.58 97 531 6.77 96 532 5.27 58 533 5.12 54534 6.79 95 535 5.0 53 536 5.91 88 537 6.76 99 538 6.77 99 539 ~5.2 54540 5.3 64 541 6.96 100 542 6.16 89 543 6.84 97 544 6.69 98 545 6.96 101546 6.69 100 547 6.75 98 548 6.79 88 549 5.75 83 550 5.74 80 551 ~5.1257 552 5.31 66 553 5.87 85 554 6.89 97 555 5.73 75 556 5.28 61 557 6.4397 558 6.73 96 559 5.22 59 560 5.43 68 561 ~5.14 56 562 6.61 97 563 6.288 564 6.58 97 566 6.42 93 568 6.89 89 569 6.68 86 570 5.38 65 571 5.8679 572 6.87 87 573 6.78 88 574 6.09 82 575 5.09 52 576 6.42 99 577 5.6367 578 6.19 92 579 5.96 83 580 6.91 108 581 6.5 93 582 6.49 103 583 5.474 584 6.87 91 585 6.95 99 586 6.28 93 587 5.48 70 588 6.22 93 589 5.0252 590 5.76 80 591 6.71 93 592 5.53 70 593 5.15 56 594 6.61 102 595 5.8783 596 6.73 102 597 ~5.37 65 598 6.68 103 599 6.95 102 600 6.38 98 6016.73 100 602 6.49 94 603 5.94 87 604 5.95 84 605 5.18 62 606 6.68 97 6076.8 102 608 6.83 98 609 6.73 99 610 5.98 87 611 ~5 46 612 5.69 74 6136.94 102 614 6.82 102 615 6.49 98 616 6.29 94 617 6.78 100 618 6.64 98619 6.73 101 620 5.4 71 621 6.21 92 622 5.8 82 623 6.84 101 624 5.65 76627 6.97 105 628 6.93 100 629 5.13 55 630 5.5 67 631 5.07 47 632 5.56 70633 5.08 56 634 5.52 68 635 6.66 97 636 5.17 59 637 6.92 99 638 6.72 100639 6.55 97 640 5.27 64 641 6.94 102 642 6.66 99 643 6.42 96 644 6.75 97645 6.56 100 646 5.93 88 647 6.2 91 648 5.59 74 649 6.8 97 650 5.87 84651 5.51 77 652 6.73 97 653 5.52 71 654 5.94 83 655 6.75 99 656 5.7 74657 6.51 97 658 5.06 52 659 ~5.08 38 660 5.65 76 661 7.23 95 662 6.52 98663 7.19 100 664 5.43 87 665 6.49 94 666 ~5.3 62 667 6.81 97 668 5.93 86669 6.77 96 670 ~5.12 56 671 5.78 76 672 6.34 92 673 5.26 61 674 6.34 94675 5.55 66 676 6.57 98 677 ~5.15 63 678 6.43 95 679 ~5.21 57 680 7.1 98681 6.53 91 682 6.94 96 683 5.38 63 684 5.37 61 685 6.07 84 686 6.74 98687 5.54 73 688 6.67 99 689 5.39 61 690 6.26 86 691 ~5.13 63 692 6.1 99693 5.01 48 694 5.61 69 695 5.23 43 696 5.77 72 697 5.23 58 698 6.6 92699 ~6.14 89 700 6.62 94 701 6.32 95 702 ~5.58 75 703 5.35 61 704 6.0686 705 5.57 71 706 ~5.63 65 707 5.19 55 708 5.73 76 709 5.39 64 710 5.5566 711 5.22 60 712 5.61 69 713 ~5.17 59 714 6.44 89 715 6.14 86 716 6.488 717 6.17 87 718 ~5.62 72 719 5.41 67 720 6.11 87 721 5.24 63 722 5.1856 723 5.1 55 724 5.38 47 725 6.61 93 726 5.71 73 727 6.69 98 728 7.19100 729 6.51 95 730 7.0 102 731 5.42 63 732 ~5.92 88 733 6.7 96 734 5.7784 735 6.87 97 736 5.38 51 737 6.52 97 738 5.72 80 739 6.63 92 740 5.0546 741 6.8 102 742 6.72 99 743 6.15 90 744 6.94 98 745 7.15 104 746 6.5694 747 7.07 96 748 6.45 99 749 6.86 97 750 6.51 94 751 6.87 98 752 6.1191 753 6.87 107 754 5.53 67 755 6.64 107 756 5.8 82 757 6.8 104 758 5.4771 759 5.04 38 760 5.32 62 761 ~5.12 45 762 6.5 95 763 ~5.27 63 764~5.36 63 765 6.44 96 766 ~5.35 67 767 5.72 76 768 5.84 79 769 5.3 60 7705.66 77 771 5.12 44 772 5.4 64 775 <5 34 776 <5 25 777 <5 34 784 <5 14785 <5 24 786 <5 31 787 <5 38 788 <5 14 789 <5 26 790 <5 47 791 <5 −2792 <5 38 793 <5 13 794 <5 −15 795 <5 34 796 <5 19 797 <5 1 798 <5 30799 <5 39 800 <5 16 801 <5 6 802 <5 24 803 <5 48 804 <5 41 805 <5 14 806<5 −6 807 <5 7 808 <5 31 809 <5 29 811 <5 35 812 <5 5 813 <5 2 814 <5 39815 <5 1 816 <5 4 817 <5 1 818 <5 2 819 <5 10 820 <5 33 821 <5 7 822 <525 823 <5 31 828 <5 4 829 <5 7 845 7.7 106 855 <5 52 859 <5 11 867 <5 44868 7.32 869 7.33 870 7.57 871 7.65 872 7.63 99 873 7.61 109 874 7.6 108875 7.6 104 876 7.51 105 877 7.47 103 878 7.44 113 879 7.38 104 880 7.1101 881 6.97 101 882 6.87 107 883 6.57 100 884 6.54 100 885 6.51 98 8865.72 79 887 5.39 73 888 <5 1 889 <5 44 890 <5 37 891 <5 8 892 <5 −29 893<5 −12 894 <5 20 895 <5 6 896 <5 10 897 <5 15 898 <5 6 899 <5 −10 900 <59 901 <5 2 902 <5 6 903 <5 15 904 <5 −24 905 <5 −7 906 <5 14 907 <5 21908 <5 2 909 <5 6 910 <5 12 911 <5 7 912 <5 1 913 <5 0.4 914 <5 1 915 <511 916 <5 20 917 <5 2 918 <5 2 919 <5 12 920 <5 35 921 <5 −7 922 <5 38923 <5 27 924 <5 41 925 <5 5 926 <5 −8 927 <5 −2 928 <5 10 929 <5 6 930<5 −14 931 <5 31 932 <5 2 933 <5 5 934 <5 27 935 <5 −2 936 <5 7 937 <5−9 938 <5 43 939 <5 2 940 <5 33 941 <5 5 942 <5 11 943 <5 9 944 <5 5 945<5 38 946 <5 37 947 <5 −14 948 <5 25 949 <5 −4 950 <5 −1.27 951 <5 41952 <5 45 953 <5 35 954 <5 27 955 <5 34 956 <5 8 957 <5 13 958 <5 −6 959<5 −7 960 <5 −2 961 <5 7 962 <5 43 963 ~4.99 62 964 ~4.96 41

Biological Example 2 Fatty Acid Synthase Keto-reductase Domain (FASN KR)Inhibition

10 μL assay buffer (100 mM KH₂PO₄ pH 7.5) was added to a 384-well clearplate (costar 3702). 0.3 μL compound (at concentrations of 30 μM, 10 μM,3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM) DMSO, 10 μL hFASNenzyme (full length, 300 ng, purified in house) and 360 μM NADPH (exceptin blank) were then added. Then, 10 μL 180 mM ethyl acetoacetate(Aldrich 688983) was added, mixed and immediately thereafter, theabsorbance at 340 nm (T1) by Multiscan (Labsystems) was measured. After20 minutes incubation at room temperature the plate was measured again(T2).

Enzymatic activity of FASN KR was measured as the oxidation of NADPH toNADP⁺ (a decrease in NADPH signal was observed at OD 340 nm,). Thedecrease in absorbance was calculated as (Absorbance before incubationT1)−(Absorbance following incubation T2).

Raw data generated by the instrument were normalized to % Controlminvalues, which were calculated as:% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and highcontrol wells on the plate, after manual exclusion of outliers. A plotof Controlmin versus test compound concentration was fitted to a4-parameter logistic curve using a non-linear least squares regressionmethod. From the plot, an IC₅₀ (concentration at such 50% inhibition isachieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀),when IC₅₀ is expressed in molar units.

Representative compounds of the present invention were tested accordingto the procedure as described in Biological Example 2 above, withresults as listed in Table 7 below.

TABLE 7 FASN Keto-reductase domain pIC₅₀ FASN Keto-reductase ID No.Domain pIC₅₀ 1 6.12 2 7.05 4 7.34 10 6.3 11 5.69 12 7.31 14 6.52 15 7.1517 6.46 19 5.5 20 6.17 27 6.92 28 7.17 29 5.63 30 6.55 31 7.45 33 7.2534 6.45 35 6.56 36 5.85 38 6.19 39 6.67 40 7.37 41 6.07 47 7.56 48 6.5549 6.81 51 6.79 52 5.75 56 5.86 57 5.77 58 7.28 59 6.88 60 6.54 63 7.0765 7.27 66 6.55 67 5.81 68 6.79 69 6.07 70 5.87 71 7.18 72 6.76 73 7.1974 7.22 75 5.67 76 6.1 77 6.06 78 6.65 79 6.49 80 5.83 81 6.73 82 5.9285 5.69 90 5.87 92 7.11 93 6.58 94 6.05 100 6.68 101 6.42 102 5.97 1036.5 105 6.3 106 6.22 112 6.69 113 5.97 114 6.63 115 6.91 200 7.46 2017.47 202 7.13 203 7.33 204 6.93 205 6.94 206 7.12 207 6.95 208 6.98 2096.59 210 6.77 211 6.7 212 7.43 213 7.12 214 7.09 215 7.61 216 7.31 2177.31 218 6.99 219 6.58 220 6.58 221 6.63 222 ~7.29 224 7.11 225 7.13 2267.62 227 6.82 228 6.95 230 6.98 231 6.55 232 6.49 233 7.03 234 7.29 2357.34 236 7.02 237 6.92 238 6.98 239 6.89 240 7.58 241 7.54 242 7.45 2437.38 244 7.25 245 7.43 246 7.42 247 7.75 248 6.83 249 7.71 250 7.16 2517.37 252 7.64 253 7.56 254 7.3 255 7.08 256 7.02 257 6.7 258 7.08 2597.53 260 7.43 261 7.05 262 7.14 263 6.6 264 6.8 265 ~7.27 266 7.33 2677.29 268 7.16 269 7.18 270 6.78 271 6.78 272 ~7.41 273 6.84 274 7.0 2787.16 279 7.35 280 6.9 281 6.96 282 6.65 283 7.03 284 7.51 286 7.22 2876.78 288 7.27 289 6.49 290 6.48 291 7.42 292 6.61 293 6.76 294 6.95 2956.98 296 7.09 297 7.21 298 7.57 299 7.23 300 6.9 301 7.56 302 7.22 3037.16 304 6.65 305 7.51 306 6.98 307 6.84 308 6.89 309 7.61 310 7.22 3117.35 312 7.12 313 7.28 314 7.09 315 6.6 316 7.12 317 7.23 318 6.91 3197.27 320 ~7.57 321 7.32 322 7.1 323 7.35 324 7.17 325 6.31 326 6.39 3276.8 328 7.1 331 6.61 332 7.22 333 6.75 334 7.36 335 6.78 336 7.16 3377.1 338 6.83 339 7.32 340 7.42 341 6.68 342 6.71 343 6.93 344 7.34 3456.64 346 7.27 347 6.92 348 7.06 349 7.23 350 7.26 351 7.21 352 7.03 3536.97 354 6.95 355 7.37 356 6.32 357 7.2 358 7.29 359 7.38 361 7.34 3626.9 365 7.27 368 7.23 369 7.43 370 7.39 371 6.89 372 7.31 374 7.45 3757.05 377 ~7.44 378 7.34 379 7.56 380 7.02 381 7.45 382 7.18 383 7.21 384~6.07 385 7.36 387 6.12 388 5.96 390 6.17 391 6.41 392 6.06 397 ~5.41398 6.02 399 5.88 400 6.32 402 6.52 404 6.31 405 6.4 406 6.44 409 6.46410 6.4 411 6.37 412 6.37 413 6.05 414 6.53 418 6.52 419 5.96 420 6.01421 5.75 423 6.26 425 6.19 426 6.15 427 5.95 428 6.23 429 6.29 431 6.33432 6.35 435 5.91 440 6.67 442 6.47 443 5.98 444 6.25 445 6.68 449 6.02450 6.19 452 6.28 453 5.95 455 6.45 457 5.84 461 5.93 462 6.04 463 6.01465 6.7 466 5.87 467 6.01 468 5.8 469 6.47 470 6.94 471 6.48 472 6.41473 6.28 474 6.74 475 6.43 476 6.21 479 6.35 480 6.28 483 6.76 484 6.59485 6.52 486 5.58 488 6.3 489 6.57 490 6.44 491 6.49 493 6.37 494 6.18495 6.14 496 6.24 497 5.56 498 6.54 499 6.32 502 5.67 507 5.44 510 5.27511 5.5 512 5.51 515 6.36 517 5.82 519 6.41 520 6.2 521 6.17 523 5.83526 5.66 528 6.21 529 6.81 530 5.53 531 6.27 534 5.86 536 5.45 537 6.37538 6.48 541 6.47 542 5.79 543 6.32 544 6.14 545 6.59 546 6.22 547 6.17548 6.78 554 6.57 557 6.37 558 6.15 562 5.86 566 6.11 576 6.17 578 5.81579 5.34 580 6.22 581 6.2 582 5.92 584 6.77 585 6.79 586 5.78 588 5.93591 5.98 594 5.97 596 6.23 598 6.51 599 6.56 600 5.92 601 6.3 602 5.81604 5.06 606 5.84 607 6.27 608 5.99 609 6.17 613 6.64 614 6.51 615 5.98616 5.81 617 6.2 618 5.95 619 6.42 621 6.29 622 5.6 623 6.63 627 6.9 6286.32 635 5.87 637 6.06 638 6.0 639 5.84 641 6.45 642 6.11 644 5.84 6456.17 647 5.86 649 6.43 652 6.46 655 6.39 657 6.18 661 6.88 662 6.21 6636.56 665 6.2 667 6.47 669 6.27 672 6.26 674 5.5 676 6.22 678 6.08 6806.65 681 5.86 682 6.74 685 5.79 686 6.17 688 6.28 690 5.99 692 5.49 6986.34 699 5.27 700 6.08 701 5.41 704 5.18 714 5.82 715 5.26 716 5.98 7175.7 720 5.19 725 6.19 727 5.96 728 6.5 729 6.09 730 6.45 733 6.27 7356.07 737 5.65 739 6.29 741 6.27 742 6.45 743 5.8 744 6.6 745 6.8 7465.97 747 6.89 748 6.28 749 6.22 750 5.94 751 6.78 752 5.98 753 6.19 7556.2 757 6.0 762 6.12 765 6.08 845 7.6 872 7.37 873 7.39 874 7.39 8757.54 876 7.44 877 7.13 878 7.22 879 7.26 880 6.95 881 6.5 882 6.53 8835.98 884 6.13 885 6.31

Biological Example 3 A2780 Ovarian Cell Proliferation Assay in LipidReduced Medium, with and without Palmitate

The biological assays described below correspond to comparative assaysfor ovarian cell proliferation. The assay procedure described belowwhich includes addition of added palmitate correspond to the controlrelative to the assay procedure which does not include addition of thepalmitate. Compounds active in the absence of palmitate would not beexpected to be active in the control.

With Palmitate:

2500 cells were seeded in a 96-well clear well plate in 200 μL RPMI1640with 10% Fetal Calf Serum (Hyclone), and incubated at 37° C., 5% CO₂.Blanks were wells without cells. The next day the culture medium wasaspirated and replaced by 160 μL culture medium with 10% Lipid-ReducedSerum (LRS, Hyclone). 20 μL test compound (at concentrations of 30 μM,10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO dilutionfollowed by 20 μL palmitate-BSA solution were added to a finalconcentrations of 0.2% DMSO, 25 μM palmitate (Sigma, P0500, 10 mM stocksolution in ethanol) 0.2% fatty-acid-free BSA, 0.25% ethanol. After 96 hincubation, an MTT assay was performed. The absorbance was measured at544 nm on a SPECTRAMAX brand microplate reader (Molecular Devices).

A best fit curve was fitted by a minimum sum of squares method, plottingControlmin versus test compound concentration. From the plot, an IC₅₀(concentration at such 50% inhibition is achieved) was calculated. pIC₅₀values, presented in the Table below, were calculated as −log(IC₅₀).

Without Palmitate:

2500 cells were seeded in a 96-well clear well plate in 200 μL RPMI1640with 10% Fetal Calf Serum (Hyclone), and incubated at 37° C., 5% CO₂.Blanks were wells without cells. The next day the culture medium wasaspirated and replaced by 160 μL culture medium with 10% Lipid-ReducedSerum (LRS, Hyclone). 20 μL test compound (at concentrations of 30 μM,10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO dilutionfollowed by 20 μL ethanol-BSA solution were added to a finalconcentrations of 0.2% DMSO, 0.2% fatty-acid-free BSA, 0.25% ethanol.After 96 h incubation an MTT assay was performed. The absorbance wasmeasured at 544 nm on a SPECTRAMAX brand microplate reader (MolecularDevices).

Raw data generated by the instrument were normalized to % Controlminvalues, which were calculated as:% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and highcontrol wells on the plate, after manual exclusion of outliers. A plotof Controlmin versus test compound concentration was fitted to a4-parameter logistic curve using a non-linear least squares regressionmethod. From the plot, an IC₅₀ (concentration at such 50% inhibition isachieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀),when IC₅₀ is expressed in molar units.

Representative compounds of the present invention were tested accordingto the procedure as described in Biological Example 3 above, withresults as listed in Table 8, below. Where a compound was tested morethan once, the IC₅₀ value listed below represents the mean of the threemeasurements. Wherein the results listed below, the pIC₅₀ value ispreceded with a “˜”, the “˜” the “˜” indicates that the standard errorof the pIC₅₀ value, as estimated by the non-linear regression algorithm,is larger than 0.5. This corresponds to a factor of uncertainly on theIC₅₀ that is larger than square root of 10 (>3.162).

TABLE 8 pIC50 Ovarian Cell, Reduced Lipid Medium With and WithoutPalmitate pIC₅₀ A2780 Ovarian pIC₅₀ A2780 Ovarian ID No. Cell, WithPalmitate Cell, Without Palmitate 1 <5 5.95 2 <5 6.01 4 5.29 7.23 10 <56.06 11 <5 ~5.52 12 5.42 ~7.44 14 <5 5.91 15 <5 ~7.2 17 <5 6.4 19 <5.215.33 20 5.09 6.19 27 <5 6.6 28 <5 6.88 29 <5 5.47 30 <5 6.42 31 <5 7.5433 <5 6.6 34 <5 6.11 35 <5 6.32 36 <5 5.46 38 <5 5.92 39 <5 6.48 40 <57.14 41 <5 5.92 47 <5 8.11 48 <5 6.74 49 <5 6.48 51 <5 6.91 52 <5 5.7356 5.22 5.8 57 <5 5.6 58 <5 6.47 59 <5 7.02 60 <5 6.58 63 <5 7.12 64 <56.2 65 <5 ~7.88 66 <5 5.96 67 <5 5.79 68 <5 6.47 69 <5 5.94 70 <5 ~5.6271 <5 7.44 72 <5 5.86 73 <5 ~7.54 74 <5 8.06 75 <5 5.23 76 <5 6.29 77 <56.18 78 <5 6.83 79 <5 6.84 80 <5 5.64 81 <5.21 6.99 82 <5 5.43 85 <5~5.54 90 <5 5.2 92 <5 7.34 93 <5 ~5.68 94 <5 ~5.67 100 <5 6.11 101 <55.77 102 <5 5.64 103 <5 6.07 105 <5 6.02 106 <5 6.13 112 <5 5.99 113 <5~5.75 114 <5 ~6.08 115 <5 ~7.21 116 ~5.52 7.45 117 5.04 ~5.62 118 <55.78 119 4.96 ~5.65 120 5.3 ~6.12 121 <5 5.66 122 ~5 6.63 124 <5 ~6.54126 <5 <5 127 5.12 6.03 133 <5 ~5.5 134 <5 5.35 137 ~5.22 ~6.07 200 <5~8.41 201 ~5.46 ~8.36 202 <5 7.23 203 <5 ~8.34 204 <5 ~7.39 205 <5 7.44206 <5 ~7.98 207 <5 7.22 208 5.22 ~7.14 209 <5 5.73 210 <5 7.28 211 <5~6.15 212 <5 8.14 213 <5 6.94 214 <5 ~7.19 215 <5 7.69 216 <5 7.2 217 <57.52 218 <5 7.07 219 5.93 7.17 220 <5 6.47 221 5.16 7.33 222 ~5.61 8.21223 5.48 ~7.7 224 ~5 8.11 225 5.28 7.6 226 <5 8.63 227 <5 7.88 228 <57.74 230 <5 6.26 231 <5.21 5.6 232 <5.21 5.62 233 <5 6.04 234 <5 ~7.54235 <5 8.0 236 <5 ~7.05 237 <5 7.45 238 <5 7.37 239 <5 7.22 240 <5.216.7 241 <5 ~7.12 242 <5 ~6.14 243 <5.21 6.19 244 <5 ~5.65 245 <5 5.81246 <5 ~8.3 247 <5 8.3 248 <5 6.29 249 <5 ~8.26 250 <5 6.52 251 <5 7.14252 <5 ~7.11 253 <5 7.92 254 <5 6.36 255 <5 ~6.01 256 <5 6.08 258 <5~7.95 259 <5 6.98 260 <5 ~7.15 261 <5 8.18 262 5.22 7.11 263 <5 6.92 264<5 7.13 265 <5 ~8.54 266 5.87 ~8.66 267 <5 8.77 268 <5 ~7.35 269 5.37~8.43 270 ~5.26 ~7.56 271 <5 ~7.13 272 <5 ~8.14 273 5.1 ~7.68 274 5.14~7.62 278 <5 ~6.16 279 <5 6.39 280 <5 ~5.71 281 <5.21 ~6.09 282 <5 ~5.68283 <5 ~5.73 284 <5 ~7.63 286 <5 ~7.67 287 <5 ~6.55 288 <5 ~6.97 289 <55.95 290 <5 ~5.71 291 <5 7.34 292 <5 6.9 293 <5 7.06 294 <5 ~5.73 295 <56.2 296 <5 ~5.68 297 <5 7.6 298 <5 7.23 299 <5 7.51 300 <5 7.13 301 <57.83 302 <5 7.88 303 <5.21 7.54 304 <5 7.07 305 <5 7.39 306 <5 7.75 307<5 7.04 308 <5 6.84 309 <5 8.21 310 <5.21 6.23 311 <5 ~6.64 313 5.067.27 316 <5 ~7.8 317 <5 7.61 318 <5 ~7.15 319 <5 ~7.87 320 5.19 7.6 3215.36 7.75 322 <5 7.83 323 <5 ~8.54 324 <5 7.71 325 <5 ~7.31 326 5.04~7.92 327 5.09 7.98 328 5 8.29 329 5.51 7.85 330 ~5.21 7.49 331 5.257.16 332 5.38 7.91 333 <5 ~7.48 334 5.16 7.62 335 <5 6.86 336 <5 7.7 3375.16 7.42 338 ~5.37 7.66 339 ~5.55 7.54 340 5.22 7.81 341 <5.21 6.88 342<5 5.73 346 <5 ~7.77 347 <5 ~7.3 348 <5 7.54 349 <5 ~7.51 350 <5 ~7.55351 5.07 7.55 352 5.52 ~6.91 353 5.22 6.61 354 <5 7.51 355 <5 7.52 356<5 ~6.79 357 <5 7.65 358 <5 8.5 359 <5.21 8.09 361 <5 ~8.44 362 <5 ~7.37363 ~5.82 ~8.19 364 6.64 ~8.53 365 ~5 8.19 366 6.25 ~8.25 368 5.35 7.67369 5.68 8.37 370 <5 ~8.62 371 5.09 7.14 372 <5 8.3 374 <5 8.0 375 <57.14 377 <5 7.64 378 <5 ~8.29 379 <5 ~8.97 380 <5 6.88 381 <5 ~8.6 382<5 ~8.17 383 ~5.33 7.98 384 5.28 7.14 385 ~5.59 ~8.44 387 <5 ~5.49 388<5 ~5.61 390 <5 ~5.58 391 <5 5.93 392 <5 5.6 397 <5 5.81 398 <5 ~5.64399 <5.21 <5.21 400 <5.21 6.64 402 <5 6.76 404 <5 5.96 405 <5 6.32 406<5 5.22 409 <5 5.68 410 <5 6.27 411 <5 6.9 412 <5 5.79 413 5.14 ~6.17414 <5 ~6.7 418 <5 ~5.67 419 <5 6.19 420 <5 ~5.68 421 <5 5.94 423 <55.89 425 <5 ~5.16 426 <5 5.63 427 <5 6.08 428 <5 ~5.96 429 <5 6.38 431<5 6.69 432 <5.21 5.82 435 <5 ~6.03 440 <5 7.02 442 <5 6.59 443 <5 6.1444 <5 ~6.68 445 <5 7.17 449 <5 ~5.02 450 <5 ~6.21 452 <5 6.2 453 <55.67 455 <5 ~6.05 457 <5.21 5.9 461 <5 ~6.37 462 <5 5.73 463 <5 ~5.42465 <5 6.74 466 <5 ~5.57 467 <5 6.12 468 <5 6.18 469 <5 7.13 470 <5~6.03 471 <5 6.38 472 <5 6.63 473 <5 ~6.56 474 <5 6.7 475 <5 6.09 476 <5~5.69 479 <5 6.16 480 <5 ~6.59 483 <5 7.32 484 <5 7.02 485 <5 ~6.91 486<5 ~5.66 488 <5 6.52 489 <5 6.83 490 <5 7.03 491 <5 7.14 493 <5 ~6.68494 <5 6.16 495 <5 6.56 496 <5 6.68 512 <5 6.0 518 ~5.39 ~5.4 520 <56.41 521 <5 ~6.47 522 <5 5.54 523 <5 6.17 524 <5 5.31 525 <5 5.31 526 <5~5.99 527 <5 ~5.71 528 <5 ~6.4 529 <5 ~7.08 530 <5 6.11 531 <5 6.83 532<5 <5 533 <5 <5 534 <5 6.11 535 5.11 5.18 536 <5 6.02 537 <5 6.58 538 ~56.88 539 <5 <5 540 5.03 5.35 541 <5 6.55 542 <5 6.08 543 <5 6.85 5445.79 7.28 545 <5 7.04 546 <5 ~6.71 547 5.23 ~6.76 548 5.21 ~6.53 549 <55.42 550 ~5 5.46 551 <5 ~5 552 <5 5.77 553 <5 5.56 554 5.11 ~6.84 555 <5~5.29 556 <5 5.23 557 5.32 6.7 558 5.2 ~6.25 559 <5 5.03 560 <5 ~5.12561 <5 <5 562 <5 6.02 563 <5 5.5 564 <5 6.28 566 <5 6.53 568 5.62 7.33569 5.66 6.69 570 <5 ~5.28 571 <5 6.01 572 <5 7.28 573 5.86 7.27 5745.24 6.06 575 <5 ~5.1 576 <5 6.54 577 <5 5.61 578 <5 6.48 579 <5 5.96580 <5 7.25 581 5.37 ~6.7 582 <5 ~6.2 583 <5 5.59 584 5.18 7.2 585 <57.08 586 <5 ~6.07 587 <5 ~5.07 588 <5 ~6.17 589 <5 5.25 590 <5 5.48 591<5 ~6.46 592 <5 5.28 593 5.02 5.17 594 <5 6.21 595 5.18 5.49 596 5.26.34 597 5.36 5.44 598 <5 6.7 599 5.26 6.84 600 <5 ~6.22 601 5.41 6.66602 5.21 6.42 603 <5 ~5.48 604 ~5 5.63 605 5.2 5.32 606 <5 5.91 607 <56.19 608 <5 6.43 609 <5 ~6.58 610 5.34 5.54 611 <5 <5 612 <5 5.42 613 <56.97 614 <5 6.77 615 <5 6.3 616 <5 5.74 617 <5 6.61 618 <5 6.1 619 <5~6.65 620 <5 ~5.32 621 5.21 6.15 622 <5 5.66 623 5.29 ~7.49 624 5.185.84 627 <5 7.92 628 <5 7.18 629 <5 5.11 630 <5 5.39 631 <5 5.23 632 <5~5.62 633 <5 5.28 634 <5 5.7 635 <5 6.89 636 <5 ~5.23 637 <5 7.07 638 <5~6.71 639 <5 ~6.44 640 <5 5.08 641 <5 ~5.65 642 <5 ~5.42 643 ~5 ~6.17644 <5 6.79 645 <5 ~5.69 646 <5 5.61 647 <5 5.71 648 <5 5.6 649 5.13 6.7650 <5 5.31 651 <5 5.56 652 <5.21 6.76 653 <5 5.38 654 <5 5.66 661 <57.37 662 <5 6.34 664 <5 ~5.54 665 <5 6.26 667 <5 ~6 672 <5 ~6.39 678 <56.17 681 <5 6.1 682 <5 6.93 683 <5 <5 685 <5 5.91 690 <5 6.15 698 <56.42 700 <5 6.33 701 <5 6.05 714 <5 6.03 716 <5 6.29 717 <5 5.79 729 <55.89 741 <5 ~5.6 742 ~5.22 ~5.6 743 <5 5.68 744 <5 ~6.67 745 <5 7.02 746<5 ~5.73 747 <5 ~7.13 748 <5 ~6.65 749 <5 5.81 750 <5 6.17 751 <5 7.05752 <5 5.79 753 <5 ~6.61 755 <5.21 ~6.5 757 <5 6.15 762 <5 ~6.01 765 <55.66 775 <5 <5 776 <5 <5 777 <5 5.02 784 <5 5.23 785 ~5.21 5.41 786 5.235.17 787 <5 5.03 788 <5 <5 789 <5 <5 790 <5 <5 791 <5.21 <5.21 792 <5 <5793 <5 <5 794 <5 <5 795 <5 <5 836 <5.52 6.43 837 <5.52 5.91 840 <5.52<5.52 842 <5.52 <5.52 844 <5.52 <5.52 845 <5 7.96 872 ~5.1 8.57 873 <57.2 874 <5 7.68 875 <5 7.87 876 <5 6.64 877 <5 7.67 878 <5 ~7.03 879 <57.6 880 <5 7.18 881 <5 6.62 882 <5 ~7.05 883 <5 ~5.61 884 <5 ~5.67 885<5 ~5.65 891 <5 <5 896 <5 <5 897 <5 <5 898 <5 <5 899 <5 <5 900 <5 <5 918<5 <5 922 <5 <5 923 <5 <5 937 <5 <5 938 <5 5.1 939 <5 <5 940 <5 <5 943<5 <5 957 <5 <5 963 <5 <5

Biological Example 4 Example 4a In Vitro LNCaP Vancouver Prostate CellProliferation Assay in Lipid Reduced Medium

LNCaP-Vancouver prostate cells were obtained from the Vancouver ProstateCancer Centre. Cells were maintained in RPMI-1640, 10% Fetal Calf Serum(FCS, Hyclone), 2 mM glutamine and 50 μg/ml Gentamicin.

For the proliferation experiment 1500 LNCaP-Vancouver cells per wellwere seeded in a 384-well black with clear bottom plate (costar 3712BC)in 40 μl RPMI-1640, 10% Lipid reduced serum (LRS, Hyclone), 50 μg/mlGentamicin and 2 mM Glutamine and incubated at 37° C., 5% CO₂. The nextday 10 μl of test compound/DMSO diluted in medium was added (3E-5M,1E-5M, 3E-6M, 1E-6M, 3E-7M, 1E-7M, 3E-8M, 1E-8M final concentration).Compounds were tested in duplicate. After 96 h incubation at 37° C., 5%CO₂ 25 μl ATP-glow mix was added. The plate was incubated for 30 min at37° C. and luminescence was measured with the Envision.

Example 4b In Vitro PC-3M-Luc-C6 Prostate Cell Proliferation Assay inLipid Reduced Medium

PC-3M-Luc-C6 prostate cells were obtained from Xenogen Corporation.Cells were maintained in MEM supplemented with 10% Fetal Calf Serum(FCS, Hyclone), 2 mM glutamine, 1 mM sodium pyruvate, 1% BME vitamins(available from for example, Sigma Aldrich), 0.1 mM non Essential AminoAcid and 50 μg/ml Gentamicin. The cells were passaged twice a week.

1000 PC-3M-Luc-C6 prostate cells (Xenogen) were seeded in a 384-wellblack with clear bottom plate (costar 3712BC) in 40 μl MEM, 10% LRS(Hyclone), 50 μg/ml Gentamicin, 2 mM Glutamine, 1 mM Sodium pyruvaat, 1%BME vitamins and 0.1 mM non Essential Amino Acid and incubated at 37°C., 5% CO₂. The next day 10 μl test compound/DMSO diluted in medium wasadded (3E-5M, 1E-5M, 3E-6M, 1E-6M, 3E-7M, 1E-7M, 3E-8M, 1E-8M finalconcentration). Compounds were tested in duplicate. After 96 hincubation at 37° C., 5% CO₂ 25 μl ATP-glow mix was added. The plate wasincubated for 30 min at 37° C. and luminescence was measured with theEnvision.

Analysis: Determination of pIC50 Values

pIC₅₀ values were calculated as follows. Raw data generated by theinstruments were normalized to % Controlmin, values, which werecalculated as:% Control_(min)=100*(x−mLC)/(mHC−mLC),

where mLC and mHC are the means of the low control wells and highcontrol wells on the plate, after manual exclusion of outliers. Therelation between the % Control_(min) values and concentration was fittedto a 4-parameter logistic curve using a non-linear least squaresregression method to determine the pIC₅₀ value. Outlying data pointswere excluded manually to get a correct fit. The pIC₅₀ corresponds to−log 10(IC₅₀), if the IC₅₀ is expressed in molar units(http://www.ncbi.nlm.nih.gov/books/NBK91994). The IC₅₀ parameter wasalways determined by non-linear regression, but one or more of the otherparameters may have been held fixed on a relevant input value, such as 0for the bottom values.

For dose response curves with FASN inhibitors in LNCaP-Vancouver orPC-3M-Luc-C6 cells the curves bottom out around 30 to 40% of the controlvalue. A standard fit PL2, forcing the lower bound to this level wasused. For those test compounds which did not exhibit FASN relatedtoxicities (but other non-target related cellular toxicity), the %control value may go to 0, and curve fit was calculated using 0% aslower bound.

Representative compounds of the present invention were tested accordingto the procedure as described in Biological Example 4a and 4b above,with results as listed in Table 9, below. Where a compound was testedmore than once, the pIC₅₀ value listed below represents the mean of themeasurements. Wherein the results listed below, the pIC₅₀ value ispreceded with a “˜”, the “˜” the “˜” indicates that the standard errorof the pIC₅₀ value, as estimated by the non-linear regression algorithm,is larger than 0.5. This corresponds to a factor of uncertainly on thepIC₅₀ that is larger than square root of 10 (>3.162).

TABLE 9 pIC50 Prostate Cell Proliferation, Reduced Lipid Medium pIC₅₀LNCaP_Vancouver pIC₅₀ PC-3M-Luc-C6 ID No. prostate cell prostate cell 2~5.71 ~6.18 39 5.98 6.82 49 6.04 6.66 59 6.58 7.0 65 7.18 ~7.61 200~7.47 8.19 201 7.68 ~8.18 202 6.26 ~7.02 203 7.67 8.25 204 6.39 7.29 2056.99 7.27 206 7.0 7.72 207 6.29 ~7.17 208 6.93 7.36 209 5.38 ~6.11 2126.96 7.74 213 6.45 ~6.95 214 6.44 7.18 215 7.15 7.8 216 6.79 ~7.27 2176.75 7.3 218 6.38 7.14 219 6.52 6.9 220 5.97 ~6.54 221 ~6.42 6.88 2227.33 8.03 223 6.62 7.22 224 7.25 7.9 225 6.8 7.57 226 7.66 ~8.23 2276.45 7.26 228 6.12 7.01 230 5.91 6.42 231 5.66 ~5.79 232 5.74 5.97 2335.77 6.24 234 6.61 7.63 236 6.19 7.29 237 6.2 ~7.13 238 6.61 7.15 2396.09 6.87 240 6.27 ~6.78 241 6.78 ~7.25 242 ~5.8 ~6.19 243 6.08 ~6.62244 5.74 ~5.85 245 ~5.77 ~6.19 246 7.81 8.32 247 7.63 8.14 248 6.32 6.58249 7.78 8.38 250 6.16 6.63 251 6.86 ~7.38 252 6.6 7.25 253 7.19 7.85254 5.86 6.65 255 5.95 ~6.28 256 5.62 ~6.38 257 6.58 7.15 258 7.5 7.84259 6.35 7.17 260 7.07 7.43 261 ~6.99 7.67 262 6.53 ~6.93 263 6.95 2646.3 7.35 265 7.86 ~8.15 266 7.82 8.33 267 7.91 ~8.51 268 6.54 7.23 2697.55 ~8.08 270 6.71 7.46 271 6.38 7.01 272 7.31 7.97 273 6.45 7.17 2746.47 7.33 282 ~5.67 ~5.77 284 7.42 7.74 286 6.91 7.6 288 6.27 7.11 290~5.67 ~5.93 291 6.53 ~7.37 292 6.16 6.75 293 ~6.29 ~6.85 294 5.69 ~6.06295 5.89 ~6.24 296 5.44 ~5.91 297 6.19 ~7.52 298 6.21 7.18 299 6.63 7.41300 5.72 6.91 301 6.56 7.92 302 6.36 7.78 303 ~6.04 7.4 304 5.9 7.14 3056.58 7.54 306 6.29 7.77 307 6.18 6.99 308 6.32 7.0 309 7.5 8.13 310 6.09~6.49 311 6.52 6.97 312 6.91 ~7.28 313 6.81 ~7.28 314 6.51 7.24 315 6.26.91 316 6.99 7.71 317 6.59 7.29 318 5.84 7.28 319 6.95 7.73 320 6.6 7.3321 6.74 7.3 322 6.82 ~7.46 323 7.48 8.08 324 6.8 ~7.52 325 6.44 7.08326 6.77 7.31 327 6.86 7.46 328 7.27 7.79 331 6.21 6.83 332 6.97 7.91333 6.27 ~6.47 334 6.79 7.43 335 6.22 ~6.94 336 6.98 337 7.1 7.69 3386.9 7.72 339 6.49 7.5 340 7.03 7.74 341 6.28 6.9 342 5.79 ~6.05 343 6.627.09 344 6.85 ~7.49 345 5.92 6.25 346 7.36 7.65 347 6.15 ~7.05 348 6.557.39 349 6.86 7.47 350 7.09 7.65 351 7.24 7.86 352 6.25 6.79 353 5.946.36 354 6.61 7.45 355 6.24 7.23 356 5.83 ~6.49 357 6.43 7.6 358 7.117.83 359 ~7.1 8.08 361 ~7.89 8.49 362 ~6.53 ~7.25 365 7.25 8.12 368 6.677.54 369 7.34 8.0 370 7.69 ~8.41 371 6.31 7.26 372 7.12 7.88 374 7.067.69 375 6.34 7.11 377 7.09 7.55 378 7.13 7.98 379 8.3 ~8.61 380 5.946.51 381 7.98 8.72 382 7.26 7.57 383 7.3 ~7.74 384 6.08 6.78 385 7.73~8.32 390 5.56 5.83 391 5.77 6.14 392 ~5.77 5.79 397 5.52 5.97 398 5.635.76 399 <5.52 <5.52 400 5.92 6.67 402 5.76 6.76 405 5.64 6.34 406 5.155.73 409 5.66 5.93 410 6.01 6.35 411 6.28 6.79 412 6.34 6.24 413 6.356.32 414 5.94 6.75 418 ~5.6 5.8 419 5.39 6.11 420 5.19 5.78 421 5.895.98 423 5.59 5.87 425 5.5 5.66 426 5.63 5.76 427 5.58 6.07 428 5.55 6.1429 5.88 6.41 432 5.69 6.06 435 5.46 5.91 440 5.94 6.63 442 5.71 6.29443 5.64 6.07 444 5.74 6.38 445 5.93 6.63 449 <5 5.62 450 5.63 6.1 4525.69 6.26 453 5.53 5.79 455 5.67 ~6.16 457 <5.52 5.66 461 ~5.6 ~6.22 4625.63 5.93 463 5.14 5.72 465 6.28 6.73 466 5.42 5.73 467 5.54 6.11 4685.69 6.26 469 6.54 7.23 470 5.83 ~6.2 471 5.89 6.54 472 5.75 6.88 4735.66 6.56 474 6.0 6.15 475 5.48 6.18 476 5.43 ~5.67 479 6.03 6.52 4805.94 6.74 483 6.42 ~7.04 484 6.26 6.82 485 6.2 6.67 486 5.35 ~5.55 4885.81 6.24 489 6.15 ~6.6 490 5.98 ~6.69 491 6.0 ~6.75 493 5.9 6.8 4945.33 6.05 495 ~5.49 ~6.23 496 5.76 ~6.45 497 5.27 6.32 498 5.61 6.63 4995.37 6.34 502 5.38 5.93 507 5.22 ~5.93 510 5.32 ~5.42 511 5.33 ~6.05 5125.4 5.88 515 5.67 6.25 517 ~5.28 5.9 519 5.57 6.26 520 5.59 6.3 521 5.726.22 523 5.49 5.93 526 5.23 5.83 528 5.63 6.3 529 6.14 ~7.08 530 5.295.91 531 5.87 6.52 534 ~5.25 6.0 536 ~5.12 ~5.51 537 5.88 6.21 538 5.71~6.69 541 ~5.99 6.51 542 5.52 5.35 543 5.7 6.59 544 6.11 6.85 545 6.576.9 546 5.82 ~6.51 547 6.0 6.27 548 5.96 6.41 554 6.19 ~6.76 557 5.866.37 558 5.6 6.14 562 5.51 5.79 566 5.81 6.24 576 5.67 6.17 578 5.3 6.06579 5.34 5.7 580 6.12 6.73 581 ~6.53 582 5.49 6.1 584 6.19 7.08 585 7.0586 5.99 588 ~6.02 591 6.43 594 5.72 ~6.23 596 5.73 ~6.12 598 5.63 ~6.45599 6.04 6.98 600 5.65 6.3 601 5.99 6.5 602 5.83 6.16 604 <5 5.38 6065.62 5.95 607 5.96 6.75 608 5.73 ~6.58 609 5.32 6.18 613 6.07 7.01 6145.87 6.42 615 5.49 ~5.63 616 5.5 <5 617 5.59 6.19 618 5.46 ~5.59 6195.49 6.2 621 5.67 6.36 622 <5 5.66 623 6.25 6.91 627 ~6.89 7.32 628 6.146.79 635 5.99 6.45 637 5.74 ~6.63 638 5.77 6.32 639 5.63 6.1 641 5.34~6.25 642 5.21 ~5.67 643 5.52 6.01 644 5.55 6.4 645 5.46 5.76 647 5.295.76 649 5.76 6.36 652 5.92 6.41 655 ~5.6 ~6.63 657 5.42 6.23 661 6.72~7.1 662 5.54 6.15 663 6.26 6.93 665 5.91 6.1 667 5.75 ~5.81 669 5.55~6.09 672 5.58 ~6.26 674 ~5.31 ~6.09 676 5.75 6.3 678 5.48 6.05 680 6.476.97 681 5.31 5.86 682 6.0 6.66 685 5.52 5.93 686 5.42 5.96 688 5.536.08 690 5.63 5.88 692 5.34 5.8 698 5.58 6.24 699 <5 5.29 700 5.47 6.0701 5.34 5.9 704 5.16 ~5.24 714 5.28 6.1 715 <5 5.3 716 5.26 5.97 7175.3 5.77 720 5.04 5.33 725 5.78 6.31 727 5.62 6.24 728 6.28 6.82 7295.06 5.84 730 ~6.39 7.01 733 5.48 5.89 735 5.42 ~6.04 737 ~5.43 6.15 7395.42 ~6.06 741 5.56 ~5.79 742 ~5.35 ~5.76 744 6.07 6.74 745 6.07 6.74746 ~5.41 ~5.78 747 6.2 7.24 748 5.52 6.24 749 5.64 6.12 750 5.5 6.23751 6.14 6.69 752 5.4 5.72 762 5.41 6.09 765 5.05 5.68 872 7.62 8.32 8736.58 7.46 875 7.06 7.98 876 6.21 6.92 877 ~6.39 7.34 879 6.42 7.51 8806.19 6.93 881 5.88 6.73 884 5.52 ~5.74 885 <5 ~5.58

Biological Example 5 ¹⁴C-acetate Incorporation in HEPG2 Liver Cells

HepG2 liver cells are obtained from the American Type CultureCollection. Cells are seeded in a 24-well plate at 7·10⁵ cells/well in400 μL MEM with 10% FCS (Hyclone). 100 μL of test compound dilution (25μM to 5 μM final) is added and plates are incubated for 4 hours at 37°C. in 5% CO₂. 50 μL of ¹⁴C-acetic acid (Acetic acid, sodium salt(1,2-14C): Amersham CFA13; 50-62 mCi/mMol, 200 μCi/ml (7.4 mBq/ml))diluted 1/50 in medium is added and plates are incubated for another 2 hat 37° C. in 5% CO₂. Medium is aspirated, and lipids are extracted fromthe cells by 3 rounds of chloroform: methanol: MgSO₄ mixture andcentrifugation steps (2 min at 10000 rpm). Each time the upper layer isremoved. Finally the remaining organic layer is evaporated undernitrogen gas, the pellet are dissolved in 500 μL heptanes and in 3 ml ofscintillation fluid added to scintillation tubes. Incorporated¹⁴C-labelled is counted in a Pachard, Tri-Carb Liquid scintillationcounter, (2 minutes)

Biological Example 6 Analysis of Intact Phospholipid Species byElectrospray Ionization Tandem Mass Spectrometry

PC-3 prostate and A2780 ovarian cells are obtained from the AmericanType Culture Collection. Cells are cultured in HamF12 or RPMI 1640respectively, supplemented with 10% FCS (Invitrogen). Palmitic acid(Sigma) is complexed to fatty acid-free bovine serum albumin(Invitrogen). Cells are cultured for 72 hours in the presence or absenceof test compound (10 μM to 0.1 μM). Xenografts are collected after 21days treatment with or without compound (100-10 mg/kg).

Tissue or cells are homogenized in 1 N HCl/CH₃OH (1:8, v/v). CHCl₃, 200μg/mL of the antioxidant 2,6-di-tert-butyl-4-methylphenol (Sigma; ref.29), and lipid standards are added. The organic fractions are evaporatedand reconstituted in CH₃OH/CHCl₃/NH₄OH (90:10:1.25, v/v/v).Phospholipids are analyzed by electrospray ionization tandem massspectrometry (ESI-MS/MS) on a hybrid quadrupole linear ion trap massspectrometer (4000 QTRAP system, Applied Biosystems) equipped with arobotic nanoflow/ion source (Advion Biosciences). The collision energyis varied as follows: prec 184, 50 eV; nI 141, 35 eV; nI 87, −40 eV;prec 241, −55 eV. The system is operated in the multiple reactionmonitoring (MRM) mode for quantification of individual species.Typically, a 3-minute period of signal averaging is used for eachspectrum. Data are corrected for ¹³C isotope effects if the contributionis >10%. Corrected data were presented as heat maps using the HeatMapBuilder software (Clifton Watt, Stanford University).

Biological Example 7 In Vivo Xenograft Assay

Animals:

Male NMRI-nude mice (obtained from Janvier) are used for the study. Micewith an initial weight of approximately 20 to 25 g are obtained. Theanimals are habituated for one week prior to any experimentalprotocols/procedures being performed.

All animals are maintained under SPF “full barrier” conditions with freeaccess to food and water. Mice are group housed under a 12-h light:darkcycle (lights on at 06:00 h) at a temperature of 19 to 22° C. and 35 to40% humidity in Techniplast type-3 IVC cages. Mice are fed a standardLaboratory chow. All experiments are carried out in accordance with theEuropean Communities Council Directives (86/609/EEC) and are approved bythe local ethical committee.

Prostate Tumor Cells:

The human PC-3 prostate tumor cells are cultured at 37° C. in ahumidified atmosphere (5% CO₂, 95% air), in F12-Ham medium supplementedwith 2 mM Sodium Pyruvate, 50 μg/ml Gentamycin, 1.5 g/l SodiumBicarbonate, 0.1 mM Non Essential Amino Acids and 10% fetal bovine calfserum. Cells are maintained as cell monolayer cultures, passaged twiceweekly at 3×10⁶ cells per T175 flask, according to the followingprocedure. Cells are washed with PBS (w/o Mg²⁺, Ca²⁺), before additionof trypsin-EDTA to the culture flasks. After detachment of cells, thetrypsin-EDTA is inactivated by addition of complete medium. The cellsuspension is then transferred to 50 ml Falcon tube and centrifuged for3 min at 1200 rpm. Medium is aspirated, with the cells beingre-suspended in an appropriate volume of complete medium. The cells arecounted in a haemocytometer and their viability is assessed by 0.25%trypan blue exclusion. An appropriate volume of cell suspension is thenadded to either a new T175 culture flask(s) or roller bottle containingfresh medium. For large scale-up growth of PC3 prostate tumor cells, anappropriate number of roller bottles are seeded with 1.2×10⁷ cells 1week prior to inoculation of the mice. The medium is changed twiceduring this period, with the last change being the day prior to cellinjection. Cells are collected as described above, with the exceptionthat after centrifugation, the cells are re-suspended in cold (4° C.)serum free medium at 5×10⁷ cells/ml.

Experimental Design:

Human PC-3 prostate tumor cells are injected directly into the inguinalregion of the male NMRI Nude mice (1×10⁷ cells/200 μl/animal) on day 0.Approximately 35 days after inoculation, when tumor volumes reach anapproximate average of 200 mm³, mice are randomized into test groupsaccording to tumor volume, and treated for 21 days with either control(no test compound) or test compound at one of three dosage levels: 10mg/kg, 30 mg/kg or 100 mg/kg.

Data Analysis:

For each individual animal, body weight and tumor size [using thecommonly accepted formula: Tumor Volume (mm³)=(a×b₂/2); where ‘a’represents the length, and ‘b’ the width of the tumor as determined bycaliper measurements], are monitored twice weekly throughout the study.A sustained body weight loss greater than 15% of the initial body weightis considered as clinical toxicity, with the animal removed from thestudy and sacrificed. Clinical signs of toxicity include, but are notlimited to, persistent anorexia or dehydration, posture, moribund,lethargy, hypothermia and/or laboured respiration (according to theUKCCCR guidelines for welfare of animals in experimental neoplasia

A time-course of tumor growth is expressed as median values, ornormalized to initial tumor volume on the day treatment started andexpressed as mean±SEM (8 to 10 animals per group). For pre-establishedtumors, relative tumor volumes is calculated for each mouse (treatedtumor volume/tumor volume on day 0) and expressed as mean±SEM for eachtreatment group. Twenty-four hours after the last treatment, animals aresacrificed, tumors excised and weighed. The anti-tumor effect of testcompound versus control is determined and represented by a bar chart ofmedian values±25/75 and 10/90 percentiles. Statistical significance isindicated by one-sided p-values from Wilcoxon-Mann-Whitney analysis(Wilcoxon rank sum test), with p<0.05 considered statisticallysignificant. Treatment/control (T/C) ratios are calculated based onfinal relative tumor volumes, using the NCI criteria—“The effectivecriteria for T/C ratios is 42%”.

Formulation Example 1 Solid, Oral Dosage Form

As a specific embodiment of an oral composition, 100 mg of the Compound#65, prepared as in Example 3, above is formulated with sufficientfinely divided lactose to provide a total amount of 580 to 590 mg tofill a size O hard gel capsule.

While the foregoing specification teaches the principles of the presentinvention, with examples provided for the purpose of illustration, itwill be understood that the practice of the invention encompasses all ofthe usual variations, adaptations and/or modifications as come withinthe scope of the following claims and their equivalents.

We claim:
 1. A compound of formula (I)

wherein R¹ and R² are taken together to form an optionally substitutedring structure selected from the group consisting of C₃₋₆cycloalkyl and4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-memberedsaturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is notpresent at the 2-position relative to the carbon atom of theimidazolidin-5-one; wherein R¹⁰ is selected from the group consisting ofhydrogen, C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxy substituted C₁₋₂alkyl),—CH₂-(phenyl), —(C₂alkyl)-O—(C₁₋₂alkyl), —C(O)—(C₁₋₄alkyl),—C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl), —C(O)O—(C₁₋₄alkyl),—C(O)—NR^(A)R^(B), and —SO₂—(C₁₋₂alkyl), wherein R^(A) and R^(B) areeach independently selected from the group consisting of hydrogen andmethyl; m is an integer from 0 to 1; and n is an integer from 0 to 2provide that when n is 2, then m is 0; such that

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl,piperidin-3S-yl, and piperidin-4-yl; a is 1; L¹ is selected from thegroup consisting of C(O)—, —C(O)O—, and SO₂—; R³ is selected from thegroup consisting of C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl,fluorinated C₁₋₂alkyl, C₂₋₄alkenyl, C₃₋₅cycloalkyl, 4 to 5-membered,saturated heterocyclyl, 5 to 6-membered heteroaryl, and NR^(V)R^(W);wherein the C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5to 6-membered heteroaryl are each optionally substituted with asubstituent selected from the group consisting of halogen, hydroxy, C₁₋₂alkyl, (C₁₋₂ alkyl)-OH, fluorinated C₁₋₂alkyl, cyano, and NH₂; andwherein R^(V) and R^(W) are each independently selected from the groupconsisting of hydrogen and methyl;

is selected from the group consisting of

b is an integer from 0 to 1; R⁴ is selected from the group consisting ofhalogen, C₁₋₂alkyl, and C₁₋₂alkoxy; R⁵ is selected from the groupconsisting of

wherein

selected from the group consisting of phenyl, naphthyl, 5 to 6-memberedheteroaryl, 9 to 10-membered heteroaryl, and partially unsaturated 9 to10-membered heterocyclyl; c is an integer from 0 to 2; each R⁶ isindependently selected from the group consisting of hydroxy, oxo,halogen, cyano, C₁₋₄ alkyl, fluorinated C₁₋₂alkyl, hydroxy substitutedC₁₋₄ alkyl, cyano-substituted C₁₋₂alkyl, —(C₁₋₂alkyl)-O—(C₁₋₂alkyl),C₁₋₄alkoxy, fluorinated C₁₋₂alkoxy, —SO₂—(C₁₋₄alkyl), —CO²H,—C(O)O—(C₁₋₂alkyl), —C(O)—(C₁₋₂alkyl), —C(O)-(fluorinated C₁₋₂alkyl),—C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₂alkyl),C₃₋₅cycloalkyl, 1-cyano-cyclopropyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl),—S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl),—NH—C(O)—(C₃-5cycloalkyl)-NH—SO₂—(C₃₋₅cycloalkyl), and oxetan-3-yl; andwherein R^(M) and R^(N) are each independently selected from the groupconsisting of hydrogen and C₁₋₂alkyl; wherein

is selected from the group consisting of phenyl and 6-membered, nitrogencontaining heteroaryl; wherein

is selected from the group consisting of phenyl, 5 to 6-membered,saturated, nitrogen containing heterocylyl and 5 to 6-membered, nitrogencontaining heteroaryl; e is an integer from 0 to 1; R⁸ is selected fromthe group consisting of halogen, C₁₋₄alkyl, C₃₋₅cycloalkyl,—(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), and oxetanyl; provided that the

is bound at the 3- or 4-position of the

relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom towhich they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and—SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl,1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or1,2,3,4-trihydro-2-methylcarbonyhisoquinolin-2-yl; provided further thatwhen R¹ and R² are taken together with the carbon atom to which they arebound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl,2-(piperazin-1-yl)-pyridin-4-yl, or2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹and R² are taken together with the carbon atom to which they are boundto form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl,1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl,indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl,6-(1-cyanomethyl)-pyridin-3-yl,6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl,3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl,4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl;provided further that when R¹and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is—C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl,benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² aretaken together with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl,1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹and R²are taken together with the carbon atom to which they are bound to formcyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl,2-oxo-3,4-dihydro-quinolin-7-yl, or6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that whenR¹and R² are taken together with the carbon atom to which they are boundto form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is aninteger from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl,benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.2. A compound as in claim 1, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl, 1-(ethenyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl, and1-(methoxycarbonyl)-azetidin-3,3-diyl; m is an integer from 0 to 1; andn is an integer from 0 to 2; provided that when n is 2 then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3R-yl, piperidin-3S-yl,and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of—C(O)—, —C(O)O— and —SO₂—; R³ is selected from the group consisting ofmethyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl,2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl,3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl,1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl,1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino,dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl,tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl,3-methyl-oxetan-3-yl, and pyridin-3-yl;

is selected from the group consisting of

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyl, and2-methoxy; R⁵ is selected from the group consisting of

wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl,3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl,2-fluoro-4-(1-cyano-cuclopropyl)-phenyl,2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl,4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl,3-(cyclopropylcarbonyl-amino)-phenyl,3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl,3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl,3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl,6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl,7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl,1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl,pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl,6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cycloprpoyl-pyridin-3-yl,6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl,5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl,1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl,1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl,1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl,quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl,quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl,2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl,2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl,2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl,2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl,2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl,3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl,4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl,2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl,2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl,3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl,6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl,3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl,3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl,quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl,1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl,1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl,1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl,1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl,2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl,1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl,1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl,1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-7-methoxymethyl-indazol-4-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-7-hydroxymethyl-indazol-4-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl,2-methyl-3-hydroxymethyl-indazol-5-yl,2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl,2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl,2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl,1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl,2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl,2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl,1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl,benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl,benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl,2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothioen-5-yl, 2,3-dihydro-benzofuran-5-yl,2-oxo-3,4-dihydro-quinolin-7-yl,1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl,1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl,2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl,1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl,2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl,pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl,[1,2,4]triazo[4,3-a]pyridin-6-yl,3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl, and4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl;

is selected from the group consisting of phenyl, pyridin-3-yl, andpyridin-4-yl; and

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl,1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl,pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl,piperazin-1-yl, 4-methyl-piperazin-1-yl, and1-(oxetan-3-yl)-pyrazol-4-yl; provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the point of attachment of the

to the

provided further that when

is pyridin-4-yl, then

is bound to

at the 3-position, relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom towhich they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and—SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl,1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl,4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl, or1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl; provided furtherthat when R¹ and R² are taken together with the carbon atom to whichthey are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is1;

is pyrrolidin-3R-yl; -(L′)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl,2-(piperazin-1-yl)-pyridin-4-yl, or2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹and R² are taken together with the carbon atom to which they are boundto form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl,1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl,indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl,5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl,6-(1-cyanomethyl)-pyridin-3-yl,6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl,3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl,4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; (L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl;provided further that when R¹and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is—C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl,benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² aretaken together with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl,1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R²are taken together with the carbon atom to which they are bound to formcyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl,2-oxo-3,4-dihydro-quinolin-7-yl, or6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that whenR¹and R² are taken together with the carbon atom to which they are boundto form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is aninteger from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl,benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.3. A compound as in claim 2, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(ethenylcarbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl, andtetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is aninteger from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3S-yl, and piperidin-4-yl; a is 1; L¹ is—C(O)—; R³ is selected from the group consisting of ethyl,1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl,3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl,cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl,1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl,cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl,oxetan-2-yl, oxetan-3yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2yl,tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and dimethylamino;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl; R⁵ is

wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl,3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl,4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl,3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl,6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl,6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl,2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl,1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl,quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl,4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl,2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl,1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl,1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl,1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl,1-oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl,indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl,1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl,1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl,2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl,1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl,1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-hydroxymethyl-indazol-5-yl,1-methyl-3-hydroxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl,benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl,benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl,benzothiazol-2-yl, benzthiazol-5-yl,5-chloro-benzothiazol-2-yl,5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl,6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl,5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl,2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl,benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl, andpyrrolo[2,3-b]pyridin-5-yl; provided that when R¹ and R² are takentogether with the carbon atom to which they are bound to form1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl or1-methyl-indazol-5-yl; provided further that when R¹ and R² are takentogether with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L′)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl, and indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl;provided further that when R¹and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹), —R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl;provided further that when R¹and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than benzoxazol-5-yl; provided further thatwhen R¹ and R² are taken together with the carbon atom to which they arebound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 2-oxo-3,4-dihydro-quinolin-7-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.4. A compound as in claim 2, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyl,cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl,1-(isopropyl)-piperidin-4,4-diyl,1-(2-hydroxy-ethyl)-piperidin-4,4-diyl,1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl,1-(methyl-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl,1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl,1-(dimethylamino-carbonyl)-piperidin-4,4-diyl,1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl,1-(methyl-sulfonyl)-piperidin-4,4-diyl,1-(2-methoxyethyl)-piperidin-4,4-diyl,1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, andtetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is aninteger from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yland piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl,cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl,tetrahydro-furan-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl; R⁵ is

wherein

is selected from the group consisting of 4-cyano-phenyl,3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl,2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl,4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl,4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl,3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl,naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl,indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl,1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl,2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl,2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl,quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl,4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl,isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl,1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl,indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl,2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl,1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl,1-methyl-3-aminocarbonyl-indazol-6-yl,1-methyl-3-methoxymethyl-indazol-5-yl,1-methyl-3-methoxymethyl-indazol-6-yl,1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl,2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl,6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl,2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl,6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl,1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl; providedthat when R¹ and R² are taken together with the carbon atom to whichthey are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and nis 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than a compound selected from the groupconsisting of quinolin-7-yl, benzofuran-5-yl and 1-methyl-indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.5. A compound as in claim 2, wherein R¹and R² are taken together to forma ring structure selected from the group consisting of cyclopropyl,cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl,1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and1-(dimethylamino-carbonyl)-piperidin-4,4-diyl; m is an integer from 0 to1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl,1-methyl-cyclopropyl, tetrahydrfuran-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro, 2-chloro, and 2-methyl; R⁵ is

wherein

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl,6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl,6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl,indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl,2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl,2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl,quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl,6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl,isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl,2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl,benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl,benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl,2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl; providedthat when R¹ and R² are taken together with the carbon atom to whichthey are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.6. A compound as in claim 2, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyland cyclopentyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl,and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro and 2-methyl; R⁵ is selected from the group consisting of

and

wherein

is selected from the group consisting of naphtha-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl,6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl,3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl,indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl,isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl,2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl,2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl, and1-methyl-benzimidazol-5-yl; wherein

and wherein

is selected from the group consisting of pyridin-4-yl and1-methyl-pyrazol-4-yl; provided that when R¹ and R² are taken togetherwith the carbon atom to which they are bound to form cyclopropyl; m is0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.7. A compound as in claim 2, wherein R¹and R² are taken together to forma ring structure selected from the group consisting of cyclopropyl,cyclopentyl, and tetrahydropyran-4,4-diyl; m is an integer from 0 to 1;and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl,1-methyl-cyclopropyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl, andoxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro and 2-methyl; R⁵ is selected from the group consisting of

is selected from the group consisting of naphth-2-yl,6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl,8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl,6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl,1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl,3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl,1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl,3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl,quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl,1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl,1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl,benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl,benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl,6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl,benzimidazol-5-yl, and 1-methyl-benzimidazol-5-yl; wherein

and wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and pyridin-4-yl;provided that when R¹and R² are taken together with the carbon atom towhich they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl, indazol-5-yl, or4-(1-isobutyl-pyrazol-5-yl)-phenyl; provided that when R¹and R² aretaken together with the carbon atom to which they are bound to formcyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹), —R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.8. A compound as in claim 2, wherein R¹ and R² are taken together toform cyclopropyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is selected from the group consisting of

b is 0; R⁵ is

wherein

is selected from the group consisting of indol-5-yl, indol-6-yl,indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl,benzofuran-5-yl, benzothien-5-yl, and 6-cyano-naphth-2-yl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.9. A compound as in claim 2, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyl,cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl,1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl,1-(isopropylcarbonyl)-piperidin-4,4-diyl, 1-(2-hydroxyethyl)-piperidin-4,4-diyl,1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl,1-(methylsulfonyl)piperidin-4,4-diyl, and1-(cyclopropylcarbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 2;and n is an integer from 0 to 1; provided that when m is 2, then n is 0;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, pyrrolidin-3R-yl, piperidin-3R-yl, and piperidin-4-yl;a is 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O— and—SO₂—; R³ is selected from the group consisting of methyl,1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl,1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl, andthiazol-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro and 2-methyl; R⁵ is

wherein

is selected from the group consisting of phenyl, pyridin-3-yl,pyridin-4-yl, and pyrazol-4-yl; and wherein

is selected from the group consisting of 4-bromo-phenyl,3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl,1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl,1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl,1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl,1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl,tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl,4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl,imidazol-1-yl, and oxetan-3-yl; provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the binding position of the

to the

provided further that when

is pyridin-4-yl or pyrazol-4-yl, then

is bound to

at the 3-position, relative to the binding position of the

to the

provided that when R¹ and R² are taken together with the carbon atom towhich they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consistingof —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and—SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopentyl; m is 1 and n is 0 or mis 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than2-(piperazin-1-yl)-pyridin-4-yl, or2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹and R² are taken together with the carbon atom to which they are boundto form cyclopropyl; m is 0, n is 0, and

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of—C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and—C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and2-methyl; then R⁵ is other than 4-(1-isobutyl-pyrazol-5-yl)-phenyl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(4-methylphenyl)phenyl or4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² aretaken together with the carbon atom to which they are bound to formcyclopropyl; m is 1, n is 1, and

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl;provided further that when R¹and R² are taken together with the carbonatom to which they are bound to form cyclopropyl; m is 0 and n is 1 or mis 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;provided further that when R¹ and R² are taken together with the carbonatom to which they are bound to form tetrahydrofuran-3,3-diyl ortetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl,pyrrolidin-3R-yl, and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from thegroup consisting of —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl; and astereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.10. A compound as in claim 8, wherein R¹ and R² are taken together toform a ring structure selected from the group consisting of cyclopropyland cyclopentyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl andpyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the groupconsisting of cyclopropyl, 1-hydroxy-cyclopropyl, and1-methyl-cyclopropyl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of2-fluoro and 2-methyl; R⁵ is

wherein

and wherein

is selected from the group consisting of pyridin-3-yl, pyridin-4-yl,1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl,1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl,1-methyl-pyrazol-5-yl, and 5-methyl-oxadiazol-2-yl; wherein

is bound to the

phenyl at the 4-position, relative to the point of attachment of the

phenyl to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable saltthereof.
 11. A compound as in claim 1, selected from the groupconsisting of5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one;6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-(4-(6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;5-(4-(benzo[d]thiazol-2-yl)-2-fluorophenyl)-6-((1-(cyclpropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;and stereoisomers, tautomers and pharmaceutically acceptable saltsthereof.
 12. A compound as in claim 1, selected from the groupconsisting of6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one;(R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-ylmethyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one;and stereoisomers, tautomers and pharmaceutically acceptable saltsthereof.
 13. A pharmaceutical composition comprising a pharmaceuticallyacceptable carrier and a compound of claim
 1. 14. A pharmaceuticalcomposition made by mixing a compound of claim 1 and a pharmaceuticallyacceptable carrier.
 15. A pharmaceutical composition comprising acompound as in claim 1 and a pharmaceutically acceptable excipient. 16.A method of treating a disorder comprising administering to a subject inneed thereof a therapeutically effective amount of a compound as inclaim 1; wherein the disorder is selected from the group consisting of(a) cancer selected from the group consisting of breast, prostate, head,neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus,stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood,and bone; (b) obesity, (c) Type II diabetes mellitus, and (d) SyndromeX.